Tetracyclic dipyrano-coumarin compounds with anti-hiv and anti-mycobacterium tuberculosis activities

ABSTRACT

The present invention relates to tetracyclodipyrano-coumarin compounds of general formula (I), wherein the substituents are defined herein. These compounds exihibit dual biological activities of anti human immunodeficiency virus type 1 (HIV-1) infection and anti- Mycobacterium Tuberculosis  (TB) infection.

CROSS REFERENCE TO RELATED APPLICATION

This application is a national phase entry under §371 based on International Application PCT/CN2007/003139, filed on Nov. 5, 2007.

FIELD OF THE INVENTION

The present invention relates to the compounds that inhibit human immunodeficiency virus type 1 (HIV-1) infection and possess anti-Mycobacterium Tuberculosis (TB) activities. The present invention also relates to the synthesis of the compounds and to the use of such compounds as effective candidate drugs for treatment of HIV-1 and/or TB infections in patients. More specifically, this invention relates to certain tetracyclic dipyrano-coumarin derivatives that possess both anti-HIV-1 and anti-TB activities.

BACKGROUND OF THE INVENTION

Acquired immunodeficiency syndrome (AIDS) caused by HIV infection is a malignant infectious disease affecting human health, and one of the leading causes of morbidity and mortility in human. Since the first case of AIDS patient was reported in USA in 1981, the FDA has approved total 22 different drugs for the treatment of AIDS patients in clinic. Even though the successful combination treatment of highly active anti-retroviral therapy (HAART) was used, most of the AIDS patients still can not be cured up to now. Because the current launched anti-HIV drugs are expensive and toxic, it is difficult for the administration of the HIV-infected patients for a long term therapy. Furthermore, the emergence of the drug resistance is frequently occurred leading that the therapy has to be ceased. Thus it is a long-sought goal of countries and pharmacologists to develop highly effective drugs against not only the wild strains but also the resistant strains of HIV with low toxic and inexpensive properties.

In 1992, researchers of national cancer institute (NCI) of USA reported 8 novel dipyrano-coumarin derivatives containing tricyclic and tetracyclic rings with anti-HIV-1 activities (J. MED. CHEM. 1992, 35, 2735), which were first isolated from a tropical rainforest plant (calophllum lanigerum) in Malaysia. Among them, the most active (+)-calanolide A (2) exihibited an EC₅₀ value of 0.1 μM and TC₅₀ value of 20 μM, repectively. The therapeutic index (TI) is within 16-279 (J. MED. CHEM. 1996, 39, 1303). When the concentration reached at 0.1 μM, (+)-calanolide A not only inhibited HIV-1 replication but also protected CEM-SS cells (human T-lymphoblastic cells) from HIV-1 attack. (+)-Calanolide A is active against the AZT-1-resistant strains (G-9106) of HIV-1 as well as the TIBO of pyridinone-resistant A17 strains. Experimental studies further demonstrated that (+)-calanolide A synergized well with the first line of nucleosides reverse transcriptase inhibitors (NRTIs) against HIV-1 such as AZT or other NNRTIs against HIV-1 in present clinical practice. Consequently, (+)-calanolide A is confirmed as a novel HIV-1 non-nucleosides reverse transcriptase inhibitor.

Recent investigation in vitro also demonstrated naturally occurring anti-HIV-1 drug calophyllum compounds to be active against TB (Bioorg. Med. Chem., 2004, 1199-1207). (+)-Calanolide A inhibited H37Rv strain growth with MIC₉₀ of 3.13 μg/mL. Many patients with AIDS died as a result from a variety of infections, in which infections caused by Mycobacterium Tuberculosis often occurred. To find a novel active compound which can directly inhibit I-IV virus and anti-TB has important significance in study of prolonging life of the patients with AIDS and reducing the death rate of the patients caused by TB infection.

In the treatment of the patients with infections of HIV and TB, current strategies, such as the therapies of HAART and antituberculosis drugs, can always result in the related side effects including nausea, vomiting, rash, abnormal liver function and the like, the therapy for HIV has to be ceased. Discontinuing treatment results in a higher probability of the virus infections. Thus, to find a pharmaceutical agent which can be used for treatment of HIV and TB infections in patients has importante significance.

Due to the low content of naturally occurring calophyllum compounds in plants, the amount of these compounds which can be extracted from the plants is very limited. It would pose a risk of destroying the environment to obtain a large amount of the compounds. Chenera and Kucherenko et al. reported the synthesis routes of racemic calanolide A, respectively (J Org Chem, 1993, 58, 5605; Tetrahedron Lett, 1995, 36, 5475). The present inventors also reported the total synthesis of racemic calanolide A and 11-demethyl calanolide A (Acta Pharmaceutica Sinica, 1999, 34 (9): 673; Chinese Chem. Lett. 1997, 8: 859, Chinese Chem. Lett. 1998, 9: 433). In 2003, the present inventors have applied for Chinese patent (Application Number: 03123628, 6, CN154849A) which described a new synthesis method by using PPA as a reaction reagent to selectively provide a key intermediate of tricyclic coumarin in large scale. In fact, it is important to identify compounds with enhanced activity by modifying the structure of compound 2, and reducing chiral centre of the structure based on the current research results.

In a further research, the present inventors found that compound 3 gave a similar activity level against HIV-1 as compared to the parent native compound (+)-calanolide A in vitro; yet compound 3 has two chiral centre carbons less, and is simpler and more convenient to synthesize. Compound 3 can be obtained from phloroglucinol as starting material through three reaction steps. Through the further structural development to compound 3, the invention has been accomplished.

DISCLOSURE OF THE INVENTION

In one aspect, the present invention relates to a compound of general formula of (I), (II) or (III), or an optically active form, pharmaceutically acceptable salt or solvate thereof, which is used as drug.

In another aspect, the present invention also relates to a process for preparing the compound of general formula (I), (II) or (III), or an optically active form, pharmaceutically acceptable salt or solvate thereof, which is used as drug.

In yet another aspect, the present invention also relates to a pharmaceutical composition comprising the compound of general formula (I), (II) or (III), an optically active form, pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier or excipient.

In yet another aspect, the present invention also relates to use of the compound of general formula (I), (II) or (III) for the manufacture of a medicament for prevention or treatment of disease resulting from HIV-1 infection including AIDS and disease resulting from Mycobacterium Tuberculosis (TB) infection.

In addition, the present invention also relates to a method for treating HIV infection and TB infection.

Specifically, in the first aspect, the invention relates to a compound of general formula (I):

or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein:

in ring C is either a carbon-carbon single bond or a carbon-carbon double bond,

in ring C is a carbon-carbon single bond or no bond;

in ring D is either a carbon-carbon single bond or a carbon-carbon double bond;

-   -   X is O or S;     -   R₁ is cyano, C₁₋₆alkyl, C₁₋₆alkyl substituted by one or more         halogen, C₃₋₆ cycloalkyl, C₁₋₆alkyl substituted by heterocyclyl,         or C₁₋₆alkyl substituted by phenyl, wherein the said phenyl         group or heterocyclic group may each be unsubstituted or         substituted by one or more substituents selected from the group         consisting of C₁₋₆alkyl, C₁₋₆alkoxyl, nitro, amino, cyano,         halogen;     -   R₂ is H, halogen, cyano, C₁₋₆alkyl, C₁₋₆ alkyl substituted by         one or more halogen, C₁₋₆alkyl substituted by phenyl, or         C₁₋₆alkyl substituted by heterocyclyl, wherein the said phenyl         group or heterocyclic group may each be unsubstituted or         substituted by one or more substituents selected from the group         consisting of C₁₋₆alkyl, C₁₋₆alkoxyl, nitro, amino, cyano,         halogen; or R₁ and R₂ together with the ring B may form a 5- or         6-member saturated alicyclic ring;     -   R₃ is H, C₁₋₆alkyl, aryl, or methylene substituted by one or         more substituents selected from the group consisting of halogen,         cyano, azido, amino, substituted amino, and substituted         aminoamide, substituted sulfonylamide, substituted ureido,         substituted thioureido, substituted guanidino groups and         substituted groups selected from aryl or alkyl;     -   R₄ is H, methyl or ethyl, with the proviso that when R₁ is         phenyl and R₂ is H, R₃ and R₄ are methyl groups where R₃ and R₄         are trans or cis; when R₄ is H and     -   in ring C is a carbon-carbon single bond, R₃ may be a dimethyl         group; furthermore, R₃ and R₄ may, together with the carbon atom         C₁₀ and C₁₁ to which they are each attached, form an additional         3-member and/or 6-member saturated carbon ring;     -   R₅ and R₆ are independently selected from the group consisting         of H, C₁₋₆alkyl, alkenyl, and phenyl group substituted with         nitro, amino, cyano, or halogen;     -   R₇ is H or C₁₋₆alkyl; R₈ is H or C₁₋₆ alkoxyl; with the proviso         that when         in ring D is a carbon-carbon single bond, R₈ is alkoxyl; when R₇         and R₈ are H,         in ring D is a carbon-carbon double bond.

Preferable compounds of general formula I and related various intermediates and by-products in their synthesis procedure are those wherein X is O, R₅ and R₆ are methyl,

in ring C is carbon-carbon single bond, and

in ring D is a carbon-carbon double bond.

Among those compounds mentioned above, more preferably, R₁ is C₁₋₆alkyl, R₂ is H or halogen, R₄ is H; wherein R₃ may be dimethyl.

In preferable compounds mentioned above, R₁ and R₂ may, together with the carbon atom to which they are attached, form an additional 5-member or 6-member ring.

Alternatively, R₁ is C₁₋₆ alkyl, R₂ is H, R₃ and R₄ may be together with each other or together with the carbon atom to which they are attached, form an additional 3-member or 6-member ring.

In another aspect, the compounds may also be the compounds of general formula (I) wherein X is O, both of R₅ and R₆ are methyl,

in ring C is a carbon-carbon double bond.

Alternatively, preferably, the compounds of general formula (I) are those in which X is S, R₄ is H, both of R₅ and R₆ are methyl,

in ring C is a carbon-carbon single bond.

Furthermore, the compound of general formula (I) may also be those in which R₁ is C₁₋₆ alkyl, R₂ is H or halogen, R₃ is methyl, R₄ is H, one of R₅ and R₆ is H and the other is C₁₋₆ alkyl, alkenyl, alkoxyl, or aryl,

in ring C is a carbon-carbon single bond.

Furthermore, when the tetracyclic coumarin compound of claim 1 in which R₃ is CH₂Br group is reacted with primary amines, a rearrangement reaction occurs leading to ring C being opened while the structure of tricyclic ring A, B, and D is unchanged, Therefore, the compounds then turn into the structure of the general formula 1′

wherein Y is selected from the group consisting of primary amine groups and substituted groups, such as C₁-C₁₀ alkyl chain, different aromatic or unaromatic ring as well as heterocyclic ring, such as isopropyl-, 2-methylene pyridine and 2-methylene furan.

The present invention also relates to a compound of general formula (II):

-   -   or an optical isomer, pharmaceutically acceptable salt or         solvate thereof,         -   wherein:         -   X id O or S;         -   R₁ is cyano, C₁₋₆ alkyl, C₁₋₆ alkyl substituted by one or             more halogen, C₃₋₆ cycloalkyl, C₁₋₆ alkyl substituted by             phenyl, or C₁₋₆ alkyl substituted by heterocyclyl, wherein             the said phenyl group or heterocyclic group may each be             unsubstituted or substituted by one or more substituents             selected from the group consisting of C₁₋₆alkyl,             C₁₋₆alkoxyl, nitro, amino, cyano, halogen;         -   R₂ is H, halogen, cyano, C₁₋₆alkyl, C₁₋₆alkyl substituted by             one or more halogen, C₁₋₆ alkyl substituted by phenyl, or             C₁₋₆alkyl substituted by heterocyclyl, wherein the said             phenyl group or heterocyclic group may each be unsubstituted             or substituted selectively by one or more substituents             selected from the group consisting of C₁₋₆alkyl,             C₁₋₆alkoxyl, nitro, amino, cyano, halogen; or R₁ and R₂             together with the ring B may form a 5- or 6-member saturated             alicyclic ring;         -   R₃ is H, C₁₋₆alkyl, aryl, or a methylene substituted by one             or more substituents selected from the group consisting of             halogen, cyano, azido, amino, substituted amino, and             substituted aminoamide, substituted sulfonylamide,             substituted ureido, substituted thioureido, substituted             guanidino groups and substituted groups selected from aryl             or alkyl;         -   R₄ is H, methyl or ethyl, with the proviso that when R₁ is             phenyl and R₂ is H, R₃ and R₄ are methyl groups where R₃ and             R₄ are trans or cis; when R₄ is H and             in ring C is a carbon-carbon single bond, R₃ can be a             dimethyl group; furthermore, R₃ and R₄ may, together with             the carbon atom C₁₋₁₀ and C₁₁ to which they are each             attached, form an additional 3-member and/or 6-member             saturated carbon ring;         -   M is H, C₁₋₄alkylacyl (alkanoyl), p-toluenesulfonyl group,             or C₁₋₄ alkyl.

The present invention also relates to a compound of general formula (III):

-   -   or an optical isomer, pharmaceutically acceptable salt or         solvate thereof,         -   wherein:         -   X is O or S;         -   R₁ is cyano, C₁₋₆ alkyl, C₁₋₆alkyl substituted by one or             more halogen, C₃₋₆ cycloalkyl, C₁₋₆alkyl substituted by             heterocyclyl, or C₁₋₆alkyl substituted by phenyl, wherein             the said phenyl group or heterocyclyl group may each be             unsubstituted or substituted selectively by one or more             substituents selected from the group consisting of             C₁₋₆alkyl, C₁₋₆alkoxyl, nitro, amino, cyano, halogen;         -   R₂ is H, halogen, cyano, C₁₋₆alkyl, C₁₋₆alkyl substituted by             one or more halogen, C₁₋₆alkyl substituted by phenyl, or             C₁₋₆alkyl substituted by heterocyclyl, wherein the said             phenyl group or heterocyclyl group may each be unsubstituted             or substituted selectively by one or more substituents             selected from the group consisting of C₁₋₆alkyl, C₁₋₆             alkoxyl, nitro, amino, cyano, halogen; or R₁ and R₂ together             with the ring B may form a 5- or 6-member saturated             alicyclic ring;         -   R₃ is H, C₁₋₆alkyl, aryl, or a methylene group substituted             by one or more substituents selected from the group             consisting of halogen, cyano, azido, amino, substituted             amino, and substituted aminoamide, substituted             sulfonylamide, substituted ureido, substituted thioureido,             substituted guanidino groups and substituted groups selected             from aryl or alkyl;         -   R₄ is H, methyl or ethyl; with the proviso that, when R₁ is             phenyl and R₂ is H, R₃ and R₄ are methyl groups where R₃ and             R₄ are trans or cis; when R₄ is H and             in ring C is a carbon-carbon single bond, R₃ may be a             dimethyl group; furthermore, R₃ and R₄ may, together with             the carbon atom C₁₀ and C₁₁ to which they are each attached,             form an additional 3-member and/or 6-member saturated carbon             ring;         -   M is H, C₁₋₄alkylacyl, p-toluenesulfonyl group or C₁₋₄             alkyl.

DEFINITIONS

As used herein, the term “optical isomers” is meant to include, when there exists an unsymmetrical carbon center in the molecule, any enantiomers, diastereomers, mixture of enantimer and diastereomers in any ratios, and racemic mixture thereof and the like.

As used herein, the term “pharmaceutically acceptable salts” means any base additional salts of a compound, which may be formed by a carboxy group present in the compound in complex with alkali metal or alkaline-earth metal such as sodium, kalium, lithium, calcium, magnesium, aluminium, etc; or with ammonia and/or organic amine group; or any acid additional salts, which may be formed by an amino group present in the compound with inorganic acids or organic acids, the inorganic acids include sulfuric acid, phosphonic acid, hydrochloric acid, hydrobromic acid, nitric acid and so on; the organic acids include oxalic acid, citric acid, maleic acid, fumaric acid, malic acid, tartaric acid, sulfonic acid and so on. The pharmaceutically acceptable salts are not limited to any particular salt.

As used herein, the term “solvate” describes a molecular complex comprising a compound of a general formula described above and an organic solvent or water, wherein the complex contains therein the organic solvent or water molecule(s); or having water or solvent molecules(s) embedded in the crystal lattices of the compound that are detectable by the analytical technology in the art. Pharmaceutically acceptable solvents suitable for purposes of the present invention include those which do not affect the biological activity of the compounds (such as water, ethanol, acetic acid, N,N-dimethylformamaide (DMF), dimethyl sulfoxide (DMSO), or any other solvents known very well or easily confirmed by those skilled in the art. The compound of the present invention can form hydrate or other solvate. It is known that hydrate is formed during freeze-drying the compound and water together, and solvate is formed by condensation of a solution of the compound in a suitable organic solvent. Consequently, both the hydrate and the solvate are also included in the present invention.

In the present invention, the term “alkyl” means both branched- and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms.

The term “alkoxyl” means an alkyl group of indicated number of carbon atoms attached through an oxygen bridge.

The term “halogen” or “halo” indicates fluoro, chloro, bromo, or iodo as substituent group; when halogen is as a substituent group, the number of substituent may be one, two or three.

The term “aryl” includes phenyl, substituted phenyl (wherein the substituted group comprises one, two or three substituent selected from the group consisting of C₁₋₆alkyl, C₁₋₆alkoxyl, cyano, nitro, or halogen).

The term “heterocyclic” as used in the present invention represents a stable 5- to 7-membered monocyclic ring, that is either saturated or unsaturated, and is consisted of carbon atoms and one to four heteroatom selected from N, O, and S; wherein the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. Preferably, the heterocyclic ring is indicated as six-membered ring such as pyridine, piperidine, piperazine, morpholine and thiomorpholine, etc.

In the present invention, when the structure formulas contain

or

or in the presence of similar sign, it is indicated that the covalent bond is located above the paper or below the paper, respectively; note that unless specified, this type of configuration is meant to be relative. Similarly, when “cis” or “trans” is referred to, they only represent the relative orientation between groups, unless specified.

In the present invention, the compounds having the sign of

in ring C represents compounds that have not been chirally resolved and are a mixture of two (or more than two) chiral isomers.

The compounds of formula (I) may also appear as either their protected forms or derivatives including those that are not specified herein. These forms or derivatives are readily apparent to those skilled in this art, all should be contained in the scope of the invention.

In yet another aspect, the present invention also relates to a process for preparing the compound of general formula (I), (II) or (III).

In addition, the present invention relates to a process for preparing a tetracyclic coumarin compound of general formula below (4 and 4′), which is characterized in that the compound with ring D is obtained from tricyclic coumarin compound with rings A, B and C under microwave irradiation as the chemical reaction below:

wherein R₁—R₈ are as defined in relation to general formula (I).

The present invention also relates to a process for preparing tetracyclocoumarin compound 4, which is characterized in that tricyclic coumarin compound 14 with rings A, B and D is reacted with acyl halide of α,β-unsaturated acid to form ring C:

wherein R₁-R₇ are as defined in relation to general formula (I).

The present invention further relates to a process for preparing the compound of general formula (I) in which X is S, which is characterized in that the compound is synthesized through the construction of ring D from tricyclic coumarin compound with rings A, B and C according to the process above:

wherein R₁—R₈ are each as defined the same as above description.

Particularly, the present invention provides a procedure for synthesis of the tetrayclic coumarin compounds through the following reaction schemes 1-6.

The purpose of the present invention is to provide a procedure (scheme 1) for synthesis of compound 4 through an improved Pechman reaction to offer coumarin (6) from phloroglucinol as starting material, characterized in that methanol saturated with dry HCl gas is used to replace usual sulfuric acid catalyst. Good yields are achieved at the room temperature for the condensation reaction of phloroglucinol with α-substituted-α-alkylacyl (alkanoyl)ethyl acetates, such as ethyl propionylacetate, ethyl butyrylacetate, ethyl benzoylacetate in the methanol containing HCl gas. According to a previous method (CN1548439A), reaction of the obtained compound 6 with crotonic acid in PPA, which acts as both a solvent and a catalyst for cyclization, gives chromenes (5a) in high yield and a minor by-product (5b). The additional characteristic is to construct ring D from compound 5a for synthesizing tetracyclic compound (4) by the aid of microwave catalysis, a new synthetic means, as shown in the following reaction scheme 1:

All compounds mentioned above are racemates. R₁-R₈ are as defined the same as above description.

Wherein the α-substituted-α-alkanoyl ethyl acetates used in Pechman reaction are obtained with the methods of:

(1) A chlorine atom is introduced at the position R₂ of the coumarin (6) by the reaction (Cabon O., Buisson D., Larcheveque M., et al. Tetrahedron Asymmetry, 1995, 6 (9): 2199-2210). Further replacement of the chlorine atom with the related reagents can introduce more diversity at the position R₂, such as replacement of the chlorine atom through the nucleophilic reagents.

(2) Reaction of malonic acid with acetone resulted in Meldrum's acid (Lermer L., Neeland E. G., Ounsworth J. P., et al. Can J Chem, 1992, 70 (5): 1427-1445). Condensation of the Meldrum's acid with any organic acid offered diversity at the α-position of the Meldrum's acid. Further, diversity is introduced at the R₁ position by reaction of phloroglucinol.

(3) Another characteristic of the present invention is to provide a chloroethyl group at the R₁ position by the improved Pechman reaction with α-chloro-α-substituted-α-alkanoyl acetic ester, such as

Chlorine atom of the chloroethyl group at the R₁ position can be replaced by various reactions to introduce more diversity, such as nucleophilic substituted reaction (as shown scheme below), Grignard reagent reaction, wittig reaction, and so on.

The present invention uses the building blocks shown below for introducing diversity at R₁ and/or R₂ position and has investigated the structure activity relationships (SARs) for anti-HIV-1 and anti-TB thereof.

2. The synthetic method of the compound of general formula I in which X is S is described as reaction scheme 2. After the compound (6) is obtained as described above, both hydroxyl groups of 6 are protected by groups such as p-methylphenylsulfonyl group to give compound 8.8 reacts with a thionating reagent to give compound 9 in which the C═O group is replaced by C═S group at the C2 position. Removal of two protective groups gave compound 10. Accordingly, construction of ring C (11) and ring D (4) is completed subsequently. The reaction is shown in the following reaction scheme 2:

3. Another purpose of the present invention is to provide a novel synthetic strategy for the compound of 4 (reaction scheme 3), characterized in that the two protecting groups of compound 8 are selectively removed under different reaction conditions. The 5-OH is selectively free at first to give compound 12, subsequently ring D is constructed to offer compound 13. Removal of the remaining protecting group gains 7-OH compound of 14, which allows constructing the ring C at the last step. To address this novel synthetic strategy, it is valuable with its regioselectivity of reaction for large-scale synthesis of chemical library in a parallel manner synthesis.

Wherein, R₁—R₇ are as defined above.

The synthesis method of the present invention is detailed as follows.

4. The specific reaction conditions of the first synthesis method of the present invention are indicated in reaction scheme 4. The compound 6 is synthesized from phloroglucinol as starting material reacted with β-keto-ethylacetate in dry HCl gas saturated methanol. The tricyclic ring compound 5 can be obtained via the described procedure above. Ring D is finally constructed to give compound 4 by microwave catalysis. When compared to the conventional method, this method has the advantages of significantly shortened reaction time, increased yield, simplified experimental operation, and being suitable for extensive parallel reaction. The reaction is shown in the following reaction scheme 4:

Wherein, R₁—R₈ are as defined as above.

In the reaction a, compound 6 is obtained from phloroglucinol according to the literature method (J. Med. Chem. 1996, 39: 1303-1313). For example, compound 6 is produced by Pechmann reaction of phloroglucinol with α-substituted-α-alkanoyl acetic esters, such as acetoacetic ester in the presence of phosphoric acid, hydrochloric acid, or sulfuric acid as catalyst. The present inventors found that compound 6 can be obtained by using methanol saturated with dry HCl gas as reaction system. The reaction can be completed at room temperature, without heating. All of the compound 6 produced is directly crystallized out of the reaction system. Thus, the target compound can be obtained by filtration, and no more purification step is necessary. Consequently, it is a preferable method. Suitable reagents for this first reaction step (a) acetoacetic ester reagents bearing corresponding R₁, R₂ substitutents, for example, ethyl acetylacetate, ethyl propionylacetate, ethyl butyrylacetate, γ-trifloro-ethyl butyrylacetate, ethyl pentanoylacetate, ethyl 4-substituted-acetylacetate, ethyl 2-substituted-acetylacetate, ethyl 2-substituted-butyrylacetate, ethyl substituted-benzoylacetate containing ethyl benzylacetate, 2-oxo-cyclopentanoic acid ethyl ester, 2-oxo-cyclohexanoic acid ethyl ester, and so on. The molar ratio between the reagents and phloroglucinol ranges from 1:1 to 1:2, with a preferable ratio being 1:1; the amount of the solvent used in the medium can be an amount just sufficient to completely dissolve the starting solid.

The reagents used in the second reaction step b consist of various corresponding substituted α,β-unsaturated organic acid, such as crotonic acid, 3,3-dimethyl acroleic acid and the like, which is reacted with coumarin compound 6 to give tricyclic compound 5 with ring A, B and C. The molar ratio between α,β-unsaturated organic acid and compound 6 is 1 ˜1.5: 1, with a preferable range of 1˜1.2: 1 and a more preferable range of 1.05: 1. Using PPA as a catalyst, the reaction temperature is maintained at 50° C.˜100° C., preferable 90° C. The reaction time is 0.5-24 h, preferable 1-10 h, and more preferably 3-5 h. The reaction conditions of b are exemplified in the CN1548439A, but the invention is not limited to those specific conditions.

The reagents used in the third reaction step c consist of substituted propenal acetals with corresponding R₅ and R₆ groups, such as 1,1-diethoxyl-3-methyl-2-butene, 1,1-diethoxyl-2-butene, 1,1-diethoxyl-2-propene, etc. The acetals are reacted with tricylic compound (5a) to obtain the final product of tetracyclic coumarin compounds 4. The molar ratio between the tricyclic intermediate (5a) and 1,1-diethoxyl-3-methyl-2-butene is 2-6:1, preferably 3-5:1, and more preferably 4:1. The present invention found that the reaction is significantly accelerated by microwave irradiation, thus the reaction time is apparently shortened. The microwave power is set up at 50-300 watt, preferable 100-200 watt, and more preferably 150 watt. The reaction temperature is 80-200° C., preferable 100-150° C., and more preferably 120° C. The irradiation time is between 10-40 minutes, preferably 20 minutes.

5. The present invention also relates to a novel synthesis method of compound (7). The characteristic of this method is that two hydroxyl groups of the compound (6) are protected by groups such as p-methylphenylsulfonyl group to give compound (8), and then the replacement of the C═O group with a C═S group by using a thionating reagent to obtain compound (9) as indicated in the reaction scheme 5.

The purpose of the first reaction step (d) is to protect both hydroxyl groups of compound (6) with some sulfonyl chlorides. The preferred protection reagents are methylsulfonyl chloride and paramethylphenylsulfonyl chloride; more preferably, paramelthylphenylsulfonyl chloride. The reaction molar ratio between sulfonyl chloride and compound (6) is 4˜10:1, preferably 5˜8:1, and more preferably 6:1.

The second reaction step e is carried out by employing thionating reagent such as P₂S₅ or Lawesson's reagent. A preferred reagent is P₂S₅. The reaction molar ratio between P₂S₅ and compound (6) is 5˜20:1, preferably 8˜15:1, and more preferably 10:1. Toluene and dimethyl benzene or other aromatic solvents are used as reaction solvent. A preferable solvent is dimethyl benzene. The reaction temperature is 60° C. to the refluxing temperature of the solvent used. The refluxing temperature of the solvent is preferred. Reaction time depends on the specific reaction; generally, it is 9-21 hours, and preferably 12 hours.

The purpose of the third reaction step f is to deprotect 5,7-ditosyl protective groups (phenolic hydroxyl group) of compound 9 by using tetrabutyl ammonium salts, such as tetrabutyl ammonium fluoride (TBAF), tetrabutyl ammonium chloride (TBAC), tetrabutyl ammonium bromide (TBAB). TBAF is preferred. The reaction molar ratio between TBAF and compound 9 may be selected depending on the specified case of the reaction. A preferred reaction molar ratio is about 2:1 and the reaction solvent is aprotic solvent with THF as a preferred solvent. The reaction temperature is from room temperature to the refluxing temperature of the solvent used. The refluxing temperature of the refluxing solvent used is preferred. The reaction time is 3-20 hours, preferably 6-15, and more preferably about 10 hours.

Both reaction steps of b and c are as the same as the description above.

In the preceding reaction scheme 5, a specific compound is used as example.

Apparently, when the corresponding groups of R₁—R₆ are as defined the same as mentioned above, the preceding synthetic objects can also be carried out.

6. The present invention further provides a novel synthetic strategy of the compounds of general formula (4). The first protective group at the 7-position of the compound (8) is selectively deprotected to give 5-OH of compound (12). The ring D is then constructed. The second protective group is subsequently removed to give 9-OH of compound (14). The ring C is built lastly as indicated in reaction scheme 6.

wherein R₁—R₈ are as defined above.

The reaction step g is to deprotect one protective group of compound 8. The two groups can be selectively removed with different reaction conditions. At room temperature, the protective group at the 5-position is deprotected in priority by using the reagent, solvent and reaction time referred to the reaction step f of synthetic scheme 5.

The second reaction step c is as the same as the previous description.

The third reaction step f is as the same as the previous description and its reaction temperature is the refluxing temperature of the solvent used.

The forth reaction step h utilizes acyl halide of α-β-unsaturated acid, such as acyl chloride of α-β-unsaturated acid. The molar ratio between the acyl chloride and compound (14) is 1˜6:1, and preferably 4:1. Lewis acid is used as catalyst and BF₃/ethyl ether solution is preferable. The reaction temperature is room temperature to the refluxing temperature of the solvent used, and is preferably the refluxing temperature of the solvent used. The reaction time is 1˜4 hours, preferably 2 hours.

In addition, when R₃ is bromomethyl group, it can be reacted with primary or secondary amines in THF at room temperature. The reaction molar ratio between amine and the corresponding bromide is 2:1. The reaction time is about 12 hours. As shown in the following reaction scheme, it illustrates that, when the reagent is a secondary amine, the reaction gives compound 15 accordingly. When the reagent is a primary amine, the structure of tricyclic ring A, B, D is unchanged and ring C happens to be opened by a rearrangement reaction to give the compound 16 and a byproduct 17, which has a 3-member saturated cyclic ring formed by R₃ at position C10 and R₄ at position C11, together with the carbon atom to which they are attached.

Y comes from various primary amines having substituted groups, such as C1-10 aliphatic chains, various aromatic or non-aromantic rings as well as heterocyclic rings. Each of Z1 and Z2 is halogen, cyano, hydroxyl, azido, benzene substituted by amino, C1-10 aliphatic chain or C1-6 alkyl, amide substituted by aryl, sulfonyl amide, ureido, thioureido and guanidino group and so on.

Because of all of the reactions mentioned above possess the characteristic of the rather mild reaction conditions, the shorten reaction time and the stable yield, the synthesis procedure in this invention is compatible with the synthesis of the chemical library by employing combinatorial method. Therefore, the procedure for synthesizing chemical library is also included in the scope of the present invention.

It is believed that one skilled in the art can modify the preceding procedure in order to improve the yield. They also can use the conventional knowledge in the art to confirm synthetic route or scheme or procedure for example, selection of the reactants, solvents and temperatures of the reaction. This modifications or variations are included in the scope of the present invention. It also can use a different conventional procedure in order to avoid some side reaction and/or improve the yield of product. This method of conventional protective groups can see for example “T. Greene, Protecting Groups in Organic Synthesis” (the Fourth Edition, John Wiley & Sons, Inc.)

The present invention relates to the pharmaceutical compositions containing the compounds at an effective, nontoxic dosage.

The present invention provides pharmaceuticals containing a therapeutically effective amount of the compounds and one or more pharmaceutically acceptable carriers and/or excipients. The carriers include saline solution, buffered saline solution, glucose, water, glycerin, ethanol and mixtures thereof, which will be illustrated in more detail in the following text. When it is necessary, the pharmaceutical composition also includes a small amount of moisture agent or emulsifying agent, or pH buffered solution. The composition can be a liquid solution, suspension, emulsion, tablet, pill, capsule, substained release formulation or powder. The composition may utilize traditional binder and carrier such as glycery tricarboxylate to prepare suppository. The formulation for oral administration concludes standard carrier such as pharmaceutically gradely mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose and magnesium carbonate and so on. The preparation of the pharmaceutical involves mixing, granulating and compressing or solubiling components, according to the need. In the additional route, the pharmaceutical composition may be prepared in nanoparticles.

The pharmaceutical carrier used may be solid or liquid.

The carriers or excipients may include time-delayed substance known in the art, such as glyceryl monostearate or glyceryl distearate, and may also include wax, ethylcellulose, hydroxypropyl methyl cellulose, and isobutenic methyl ester and so on. When the formulation is used for oral administration, 0.01% Tween 80 in PHOSALPG-50 (condensate of phospholipid and α-propylene-glycol (1,2-propanediol), A Nattermann & Cie.GmbH), in which is used for the preparation of acceptable oral formulation of other compounds. The formulations for oral administration are suitable for all of the compounds in the present invention.

The present invention also relates to a method for treatment of HIV infection and/or TB infection.

The present invention relates to the compounds and use of said compounds for treating viral infections caused by a broad-spectrum of viruses in mammals. In particular, the present invention is suitable for treating viral infection caused by retrovirus. More specifically, the present invention relates to the compounds which selectively inhibit HIV replication.

The present invention relates to the compounds and use of said compounds for treatment of mycrobacteria infection caused by TB in mammals. In particular, the present invention is also suitable for the treatment of tuberculosis disease caused by TB.

The compounds of the present invention can be used in a variety of pharmaceutical forms. If solid carrier is used, the pharmaceutical in formulation can be a tablet form, powder form put into hard capsule, pill form, pastille form or (sugar) lozenge form. The amount of solid carrier can be variable, and preferably will be selected from about 25 mg to about 1.0 g per dosage. If liquid carrier is used, the formulation will be in the form of syrup, emulsion, soft capsule or sterile injectable solution or suspension in non-aqueous suspension in the ampule or the vial.

A various of release systems is known and may use for administration of the compound or any formulations thereof. These formulations include tablet, capsule, injectable solution, capsule in liposome, microparticler, microcapsule and so on.

The method of administrations include but not limited to subcutaneous, intracutaneous, intramuscular, intraperitoneal, intravenous, hypodermatic, intranasal, intrapulmonary, epidural, intraocular route, but preferably oral administration. The compound may be adminstered by any convenient or other suitable route, such as by injection, or bolus, to be absorbed via epithelial route or mucosal route (eg. oral mucosa, rectal mucosa and intestinal mucosa and so on) or through a carrier or matrix-loaded drug, or adminstered together with other biological active agents. The administrations of drugs may be the whole or the topical administration. When it is used for the treatment or prevention of nasal-, bronchial-, or lung-diseases, preferable administration is oral, nasal, or bronchial, aerosol, or sprayer.

EXAMPLES

The following examples are illustrative of the invention but do not deem to limit their scope.

Experimental

Melting points were uncorrected and were determined with Yanaco micromelting point apparatus. Microwave reaction was conducted with a CEM Discover Explorer Microwave Reaction Synthesizer. MS spectra were recorded with an Finnigan LCQ-Advantage spectrometer. Infrared spectra were recorded with an Impaco 400FI-IR spectrometer (KBr). ¹H NMR spectra were recorded with ARX-300, -400 NMR spectrometers. Elemental analyses were performed with a Carlo-Erba 1106 elemental analyzer. High resolution MS spectra were recorded with a Agilent LC-MSD/TOF mass spectrometer.

Example 1 4,6,6,10-tetramethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-1, R₁═R₃═R₅═R₆═CH₃, R₂═R₄═H)

(1) 4-methyl-5,7-dihydroxy-coumarin (6-1, R₁═CH₃, R₂═H)

To a mixture of 7.5 g (0.046 mol) phloroglucinol and 6.0 g (0.046 mol) acetoacetic ester was added 50 ml methanol saturated with dry hydrochloride gas. The reaction mixture was stirred until phloroglucinol was dissolved under the room temperature, the reaction solution was kept three days at room temperature. The solid product was collected by filtration to obtain 8.5 g of the title compound as a white powder. Yield, 96%; m.p. 282-284° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.497 (s, 1H, OH), 10.275 (s, 1H, OH), 6.241 (d, 1H, J=2.4 Hz, 8-H), 6.147 (d, 1H, J=2.4 Hz, 6-H), 5.822 (s, 1H, 3-H), 2.468 (s, 3H, 4-CH₃);

ESI-MS (m/z): 193.1 [M+H]⁺ (MW=192.17);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-2,10-dione (5a-1, R₁═R₃═CH₃, R₂═R₄═H) or benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-2,6-dione (5b-1, R₁═R₃═CH₃, R₂═R₄═H).

To a fine mixture of 1.92 g (10 mmol) 4-methyl-5,7-dihydroxyl-coumarin and 0.92 g (10.7 mmol) crotonic acid was added 50 ml polyphosphate (PPA) with stirring at 90° C. for 3 hours. The reaction mixture was poured into ice-water with vigorous stirring. A yellow solid powder obtained and was filtrated, washed with water and dried. The solid obtained was separated with silica-gel column chromatography with petroleum ether/ethyl acetate as the eluent to give the 1.6 g of the title compound 5a-1 (yield, 62%, m.p. 264-266° C.) as a white powder and 5b-1 (yield, 10%, m.p. 210-211° C.) as a white powder.

Compound 5a-1 ¹H NMR (300 MHz, DMSO-d₆, ppm): 11.687 (s, 1H, OH), 6.277 (s, 1H, 6-H), 6.056 (s, 1H, 3-H), 4.637 (m, 1H, 8-H), 2.680 (dd, 1H, J=5.4 Hz, 16.2 Hz, 9-He), 2.592 (dd, 1H, J=2.4 Hz, 16.2 Hz, 9-Ha), 2.478 (s, 3H, 4-CH₃), 1.388 (d, 3H, J=6.3 Hz, 8-CH₃); ESI-MS (m/z): 261.1 [M+H]⁺ (MW=260.25);

Compound 5b-1 ¹H NMR (300 MHz, DMSO-d₆, ppm): 13.724 (s, 1H, OH), 6.450 (s, 1H, 10-H), 5.971 (s, 1H, 3-H), 4.620 (m, 1H, 8-H), 2.780 (m, 2H, 7-CH₂), 2.620 (s, 3H, 4-CH₃), 1.550 (d, 3H, J=6.3 Hz, 8-CH₃); ESI-MS (m/z): 261.1 [M+H]⁺ (MW=260.25);

(3) 4,6,6,10-tetramethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-1, R₁═R₃═R₅═R₆═CH₃, R₂═R₄═H)

To a solution of benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-2,10-dione

(5a-1) (26 mg, 0.1 mmol) in 5 ml toluene. 1,1-diethoxyl-3-methyl-2-butene (63 mg, 0.4 mmol) in 1 ml pyridine was added. The reaction solution was irradiated with microwave at 150 watt, 120° C. for 20 min. The resulting reaction was diluted with dichloromethane (DCM) and then washed with 5% HCl (3 20 ml), saturated NaHCO₃ (3 20 ml) and NaCl (3 20 ml) sequentially. The above DCM solution was dried over dry MgSO₄ and concentrated in vacuo to give viscous solid, which was purified by silica-gel column chromatography with petroleum ether/ethyl acetate as the eluent to afford 27 mg of the title compound in 83% yield as a off-white powder, m.p. 213-215° C.

¹HNMR (300 MHz, DMSO-d₆, ppm): 6.640 (d, 1H, J=9.9 Hz, 8-H), 6.030 (s, 1H, 3-H), 5.600 (d, 1H, J=9.9 Hz, 7-H), 4.640 (m, 1H, 10-H), 2.690 (m, 2H, 11-CH₂), 2.560 (s, 3H, 4-CH₃), 1.550, 1.540 (2s, 6H, CH₃), 1.520 (d, 3H, J=6.3 Hz, 10-CH₃);

ESI-MS (m/z): 327.1 [M+H]⁺ (MW=326.35); I

R (KBr, cm⁻¹): 1726, 1685, 1608, 1558, 1336, 1245, 1118, 1082, 885;

Element analysis: Calculated for C₁₉H₁₈O₅ (%): C, 69.93; H, 5.56. Found (%): C, 69.63; H, 5.53.

Example 2 3,4,6,6,10-pentamethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4−2, R₁═R₂═R₃═R₅═R₆═CH₃, R₄═H)

(1) 3,4-dimethyl-5,7-dihydroxy-coumarin (6-2, R₁═R₂═CH₃)

Using the procedure the same as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) pholoroglucinol and 6.63 g (0.046 mol) 2-methyl-acetoacetic ester as starting material to obtain 9.2 g of the title compound in 97% yield as a white powder crystalline. Yield, 97%, m.p. 235-237° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.377 (s, 1H, 7-OH), 10.105 (s, 1H, 5-OH), 6.249 (d, 1H, J=2.4 Hz, 8-H), 6.127 (d, 1H, J=2.4 Hz, 6-H), 2.503 (s, 3H, 4-CH₃), 1.982 (s, 3H, 3-CH₃); ESI-MS (m/z): 207.1 [M+H]⁺ (MW=206.20);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-3,4,8-trimethyl-2,10-dione (5a-2, R₁═R₂═R₃═CH₃, R₄═H)

Using the procedure the same as described in the preparative method of compound 5a-1, except for using 2.06 g (10 mmol) 3,4-dimethyl-5,7-dihydroxyl-coumarin (6-2) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.25 g ot the title compound in 82% yield as a yellowish powder. m.p. 168-170° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 11.570 (s, 1H, OH), 6.263 (s, 1H, 6-H), 4.617 (m, 1H, J=6.3 Hz, 3.9 Hz, 11.1 Hz, 8-H), 2.636 (dd, 1H, J=11.1 Hz, 16.2 Hz, 9-He), 2.543 (dd, 1H, J=3.9 Hz, 16.2 Hz, 9-Ha), 2.489 (s, 3H, 4-CH₃), 2.010 (s, 3H, 3-CH₃), 1.380 (d, 3H, J=6.31 Hz, 8-CH₃);

ESI-MS (m/z): 275.1 [M+H]⁺ (MW=274.27);

Element analysis: Calculated for C₁₅H₁₄O₅.4/3H₂O (%): C, 60.39; H, 5.63. Found (%): C, 60.21; H, 5.59.

(3) 3,4,6,6,10-pentamethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-2, R₁═R₂═R₃═R₅═R₆═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 27 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-3,4,8-trimethyl-2,10-dione (5a-2) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 27 mg of the title compound in 79% yield as off-white solid, m.p. 142-144° C.

¹H-NMR (400 MHz, DMSO-d₆): 6.557 (d, 1H, J=10.0 Hz, 8-H), 5.762 (d, 1H, J=10.0 Hz, 7-H), 4.717 (m, 1H, 10-H), 2.696 (dd, 1H, J=12.4 Hz, 16.4 Hz, 11-He), 2.594 (dd, 1H, J=2.8 Hz, 16.4 Hz, 11-Ha), 2.515 (s, 3H, CH₃), 2.029 (s, 3H, CH₃), 1.433 (s, 6H, 6-CH₃), 1.478 (d, 3H, J=6.0 Hz, 10-CH₃);

ESI-MS (m/z): 341.1 [M+H]⁺ (MW=340.38);

Element analysis: Calculated for C₂₀H₂₀O₅.5/6 H₂O (%): C, 67.59; H, 6.14. Found (%): C, 67.37; H, 6.04.

Example 3 4,6,6,10-tetramethyl-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-di one (4-3, R₁═R₃═R₅═R₆═CH₃, R₂═Cl, R₄═H)

(1) 3-chloro-4-methyl-5,7-dihydroxy-coumarin (6-3, R₁═CH₃, R₂═Cl)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 5.57 g (0.046 mol) 2-chloro acetoacetic ester as starting material to obtain 9.8 g of the title compound in 94% yield as a white powder crystalline. m.p. >300° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.762 (s, 1H, 7-OH), 10.433 (s, 1H, 5-OH), 6.312 (d, 1H, J=2.8 Hz, 8-H), 6.195 (d, 1H, J=2.8 Hz, 6-H), 2.682 (s, 3H, 4-CH₃);

ESI-MS (m/z): 227.1 [M+H]⁺ (MW=226.62)

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-3-chloro-2,10-dione (5a-3, R₁═R₃═CH₃, R₂═C, R₄═H) and benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-3-chloro-2,6-dione (5b-3, R₁═R₃═CH₃, R₂═Cl, R₄═H).

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.26 g (10 mmol) 3-chloro-4-methyl-5,7-dihydroxy-coumarin (6-3) and 0.92 g (10.7 mmol) of crotonic acid as starting material to obtain 2.3 g of the title compound 5a-3 in 78% yield as a white powder m.p. 151-153° C. as well as 0.28 g of the title compound 5b-3 in 10% yield as a white powder m.p. 179-180° C.

Compound 5a-3: ¹H NMR (300 MHz, DMSO-d₆, ppm): 11.931 (s, 1H, OH), 6.329 (s, 1H, 6-H), 4.655 (m, 1H, 8-H), 2.713 (s, 3H, 4-CH₃), 2.658 (dd, 1H, J=11.4 Hz, 16.5 Hz, 9-He), 2.599 (dd, 1H, J=3.9 Hz, 16.5 Hz, 9-Ha), 1.394 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 295.1 [M+H]⁺ (MW=294.69);

Element analysis: Calculated for C₁₄H₁₁ClO₅ (%): C, 57.06; H, 3.76. Found (%): C, 56.88; H, 3.80.

Compound 5b-3: ¹H-NMR (400 MHz, DMSO-d₆, ppm): 13.986 (s, 1H, OH), 6.527 (s, 1H, 10-H), 4.765 (m, 1H, 8-H), 2.999 (dd, 1H, J=12.4 Hz, 17.2 Hz, 7-He), 2.821 (dd, 1H, J=3.2 Hz, 17.2 Hz, 7-Ha), 2.720 (s, 3H, 4-CH₃), 1.443 (d, 3H, J=6.4 Hz, 8-CH₃);

ESI-MS (m/z): 295.1 [M+H]⁺ (MW=294.69);

(3) 4,6,6,10-tetramethyl-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-3, R₁═R₃═R₅═R₆═CH₃, R₂═Cl, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-3-chloro-2,10-dione (5a-3) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 31 mg of the title compound in 86% yield as off-white powder, m.p. 141-143° C.

¹H-NMR (400 MHz, DMSO-d₆): 6.585 (d, 1H, J=10.0 Hz, 8-H), 5.815 (d, 1H, J=10.01 Hz, 7-H), 4.733 (m, 1H, 10-H), 2.775 (dd, 1H, J=12.0 Hz, 16.4 Hz, 11-He), 2.706 (s, 3H, 4-CH₃), 2.641 (dd, 1H, J=3.2 Hz, 16.4 Hz, 11-Ha), 1.510, 1.474 (2s, 6H, 6-CH₃), 1.452 (d, 3H, J=6.4 Hz, 10-CH₃);

ESI-MS (m/z): 361.1 [M+H]⁺ (MW=360.80);

Element analysis: Calculated for C₁₉H₁₇ClO₅.2/3H₂O (%): C, 61.21; H, 4.96. Found (%): C, 61.36; H, 5.12.

Example 4 4,6,6,10-tetramethyl-3-benzyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-d ione (4-4, R₁═R₃═R₅═R₆═CH₃, R₂═CH₂C₆H₅, R₄═H)

(1) 3-benzyl-4-methyl-5,7-dihydroxy-coumarin (6-4, R₁═CH₃, R₂═CH₂C₆H₅)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 10.2 g (0.046 mol) 2-benzyl acetoacetic ester as starting material to obtain 12.1 g of the title compound in 92% yield as a white powder crystalline. m.p. 256-257° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.469 (s, 1H, 7-OH), 10.202 (s, 1H, 5-OH), 7.228 (m, 5H, Ph), 6.271 (d, 1H, J=2.4 Hz, 8-H), 6.165 (d, 1H, J=2.4 Hz, 6-H), 3.874 (s, 2H, 3-CH₂), 2.513 (s, 3H, 4-CH₃);

ESI-MS (m/z): 283.0 [M+H]⁺ (MW=282.30);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-3-benzyl-4,8-dimethyl-2,10-dione (5a-4, R₁═R₃═CH₃, R₂═CH₂C₆H₅, R₄═H) and benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-diimethyl-3-benzyl-2,6-dione (5b-4, R₁═R₃═CH₃, R₂═CH₂C6H₅, R₄═H).

Using the same procedure as described in the preparative method of compound 5a-1 in example 1, except for using 2.82 g (O₁ mmol) 2-benzyl-4-methyl-5,7-dihydroxyl-coumarin (6-4) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.3 g of the title compound 5a-4 in 66% yield as a white powder m.p. 172-174° C. as well as 0.6 g of the title compound 5b-4 in 17% yield as a white powder m.p. 198-199° C.

Compound 5a-4: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.230 (m, 5H, 3-CH₂-Ph), 6.304 (s, 1H, 6-H), 4.645 (m, 1H, 8-H), 3.913 (s, 2H, 3-CH₂-Ph), 2.587 (m, 2H, 9-CH₂), 2.517 (s, 3H, 4-CH₃), 1.387 (d, 3H, J=6.6 Hz, 8-CH₃);

ESI-MS (m/z): 351.1 [M+H]⁺ (MW=350.37);

Elemental analysis: Calculated for C₂₁H₁₈O₅.1/2H₂O (%): C, 70.19; H, 5.32. Found (%): C, 70.32; H, 5.02.

Compound 5b-4: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 13.958 (s, 1H, 5-OH), 7.239 (m, 5H, 3-CH₂-Ph), 6.468 (s, 1H, 10-H), 4.739 (ddq, 1H, J=6.3 Hz, 3.3 Hz, 12.3 Hz, 8-H), 3.916 (s, 2H, 3-CH ₂-Ph), 2.982 (dd, 1H, J=17.4 Hz, 12.3 Hz, 7-He), 2.799 (dd, 1H, J=17.4 Hz, 3.3 Hz, 7-Ha), 2.565 (s, 3H, 4-CH₃), 1.437 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 351.1 [M+H]⁺ (MW=350.37);

Elemental analysis: Calculated for C₂₁H₁₈O₅ (%): C, 71.99; H, 5.18. found (%): C, 71.87; H, 5.15.

(3) 4,6,6,10-tetramethyl-3-benzyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-4, R₁═R₃═R₅═R₆═CH₃, R₂═CH₂C₆H₅, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 35 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-3-benzyl-4,8-dimethyl-2,10-dione (5a-4) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 34 mg of the title compound in 82% yield as off-white powder, m.p. 158-159° C.

¹H-NMR (400 MHz, DMSO-d₆): 7.199 (m, 5H, 3-CH₂-Ph), 6.587 (d, 1H, J=10.0 Hz, 8-H), 5.776 (d, 1H, J=10.0 Hz, 7-H), 4.708 (m, 1H, 10-H), 3.951 (s, 2H, 3-CH ₂), 2.726 (dd, 1H, J=12.0 Hz, 16.8 Hz, 11-He), 2.631 (dd, 1H, J=3.2 Hz, 16.8 Hz, 11-Ha), 2.550 (s, 3H, 4-CH₃), 1.486, 1.455 (2s, 6H, 6-CH₃), 1.448 (d, 3H, J=5.6 Hz, 10-CH₃);

ESI-MS (m/z): 417.1 [M+H]⁺ (MW=416.48);

Elemental analysis: Calculated for C₂₆H₂₄O₅.2/3H₂O (%): C, 72.88; H, 5.96. found (%): C, 72.57; H, 5.86.

Example 5 6,6,10-trimethyl-4-chloromethylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-5, R₁=ClCH₂, R₂═R₄═H, R₃═R₅ s═R₆═CH₃)

(1) 4-chloromethylene-5,7-dihydroxy-coumarin (6-5, R₁═ClCH₂, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 7.6 g (0.046 mol) 4-chloro acetoacetic ester as starting material to obtain 10 g of the title compound in 96% yield as a white powder crystalline. m.p. 228-230° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.881 (s, 1H, 7-OH), 10.414 (s, 1H, 5-OH), 6.273 (d, 1H, J=2.4 Hz, 8-H), 6.211 (d, 1H, J=2.4 Hz, 6-H), 5.023 (s, 2H, 4-CH₂);

ESI-MS (m/z): 227.1 [M+H]⁺ (MW=226.62);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-chloromethylene-2,10-dione (5a-5, R₁=ClCH₂, R₂═R₄═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.26 g (10 mmol) 4-chloromethylene-5,7-dihydroxy-coumarin (6-5) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.5 g of the title compound 5a-5 in 85% yield as a yellowish powder, m.p. 230-233° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.496 (s, 1H, 6-H), 6.124 (s, 1H, 3-H), 5.724 (s, 2H, 4-CH₂—Cl), 4.707 (m, 1H, 8-H), 2.664 (m, 2H, 9-CH₂), 1.425 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 295.0 [M+H]⁺ (MW=294.69);

(3) 6,6,10-trimethyl-4-chloromethylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-d ione (4-5, R₁═ClCH₂, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-chloromethylene-2,10-dione (5a-5) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene to obtain 29 mg of the title compound in 80% yield as off-white powder, m.p. 132-134° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.587 (d, 1H, J=10.2 Hz, 8-H), 6.507 (s, 1H, 3-H), 5.820 (d, 1H, J=10.2 Hz, 7-H), 4.998 (s 2H, 4-CH₂Cl), 4.720 (m, 1H, 10-H), 2.668 (m, 2H, 11-CH₂), 1.527, 1.492 (2s, 6H, 6-CH₃), 1.450 (d, 3H, J=6.3 Hz, 10-CH₃);

ESI-MS (m/z): 361.1 [M+H]⁺ (MW=360.79);

Elemental analysis: Calculated for C₁₉H₁₇ClO₅ (%): C, 63.25; H, 4.75. Found (%): C, 63.23; H, 4.87.

Example 6 6,6,10-trimethyl-4-piperazidinylmethylene-10,11-dihydro-6H-benzo[2,3-f:2′,3′-h]-tripyranyl-2,12-dione (4-6, R₁=piperazidinylmethylene, R₂═R₄═H, R₃═R₅═R₆═CH₃)

36 mg (0.1 mmol) 6,6,10-trimethyl-4-chloromethylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-d ione was reacted with 17 mg (0.2 mmol) piperazidine for 10 hours at room temperature, after purification by silica-gel column chromatography, the title compound 4-6 was obtained in 64% yield as off-white powder, m.p. 156-158° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 6.857 (s, 1H, NH), 6.576 (d, 1H, J=10.0 Hz, 8-H), 6.467 (s, 1H, 3-H), 5.786 (d, 1H, J=10.0 Hz, 7-H), 4.712 (m, 1H, 10-H), 4.309 (m, 4H, CH₂), 3.754 (s, 2H, 4-CH₂), 3.430 (m, 4H, CH₂), 2.754 (dd, 1H, J=11.6 Hz, 16.4 Hz, 11-He), 2.642 (dd, 1H, J=3.6 Hz, 16.4 Hz, 11-Ha), 1.502, 1.468 (2s, 6H, 6-CH₃), 1.444 (d, 3H, J=6.4 Hz, 10-CH₃);

ESI-MS (m/z): 411.2 [M+H]⁺ (MW=410.47);

High-resolution electrospray ionization mass spectrometry (HRESIMS): Calculated for C₂₃H₂₇N₂O₅ ⁺ (m/z): 411.19199, Found (m/z): 411.1921.

Example 7 6,6,10-trimethyl-4-p-methylpiperazidinylmethylene-10,11-dihydro-6H-[2,3-f:2′,3′-h]-tri pyranyl-2,12-dione (4-7, R₁=p-methylpiperazidinylmethylene, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-6, except for using 36 mg (0.1 mmol) 6,6,10-trimethyl-chloromethylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-5, R₁=ClCH₂, R₂═R₄═H, R₃═R₅═R₆═CH₃) and 20 mg (0.2 mmol) p-methylpiperazidine as starting material to obtain 32 mg of the title compound 4-7 in 75% yield as off-white powder, m.p. 238-239° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 6.633 (d, 1H, J=10.0 Hz, 8-H), 6.597 (s, 1H, 3-H), 5.605 (d, 1H, J=10.0 Hz, 7-H), 4.644 (m, 1H, 10-H), 3.974 (s, 2H, 4-CH₂), 3.653 (m, 4H, CH₂), 2.977 (m, 4H, CH₂), 2.891 (s, 3H, N—CH₃), 2.698 (m, 2H, 11-CH₂), 1.546, 1.523 (2s, 6H, 6-CH₃), 1.254 (d, 3H, J=6.4 Hz, 10-CH₃);

ESI-MS (m/z): 425.2 [M+H]⁺ (MW=424.50);

HRESIMS: Calculated for C₂₄H₂₉N₂O₅ ⁺ (m/z): 425.20764, found (m/z): 425.2077.

Example 8 6,6,10-trimethyl-4-trifluoromethyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-8, R₁═CF₃, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-trifluoromethyl-5,7-dihydroxy-coumarin (6-8, R₁═CF₃, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 8.47 g (0.046 mol) 4,4,4-trifluoro acetoacetic ester as staring material to obtain 10.4 g of the title compound in 92% yield as a yellow powder crystalline. m.p. 212-214° C.;

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.901 (s, 1H, 7-OH), 10.654 (s, 1H, 5-OH), 6.523 (s, 1H, 3-H), 6.313 (d, 1H, J=2.4 Hz, 6-H), 6.276 (d, 1H, J=2.4 Hz, 8-H);

ESI-MS (m/z): 247.1 [M+H]⁺ (MW=246.14);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-tri fluoromethyl-8-methyl-2,10-dione (5a-8, R₁═CF₃, R₂═R₄═H, R₃═CH₃) and benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-trifluoromethyl-8-methyl-2,6-dione (5b-8, R₁=

CF₃, R₂═R₄═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.47 g (10 mmol) 4-trifluoromethyl-5,7-dihydroxy-coumarin (6-8) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 1.8 g of the title compound 5a-8 in 58% yield as a yellowish powder (m.p. 121-123° C.) and 0.38 g of the title compound 5b-8 in 12% yield as a yellowish powder (m.p. 159-160° C.).

Compound 5a-8: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 12.108 (s, 1H, OH), 6.774 (s, 1H, 3-H), 6.340 (s, 1H, 6-H), 4.687 (qt, 1H, J=6.3 Hz, 4.2 Hz, 10.5 Hz, 8-H), 2.694 (dd, 1H, J=10.5 Hz, 16.2 Hz, 9-He), 2.623 (dd, 1H, J=4.2 Hz, 16.5 Hz, 9-Ha), 1.405 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 315.1 [M+H]⁺ (MW=314.22)

Elemental analysis: Calculated for C₁₄H₉F₃O₅ (%): C, 53.51; H, 2.89. Found (%): C, 53.41; H, 3.04.

Compound 5b-8: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 13.975 (s, 1H, OH), 6.799 (d, 1H, J=0.9 Hz, 3-H), 6.600 (d, 1H, J=1.8 Hz, 10-H), 4.806 (qt, 1H, J=6.3 Hz, 3.3 Hz, 12.3 Hz, 8-H), 3.017 (dd, 1H, J=12.3 Hz, 17.7 Hz, 7-He), 2.828 (dd, 1H, J=3.3 Hz, 17.7 Hz, 7-Ha), 1.451 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 315.1 [M+H]⁺ (MW=314.22)

(3) 6,6,10-trimethyl-4-trifluoromethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-di one (4-8, R₁═CF₃, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 31 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-trifluoromethyl-8-methyl-2,10-dione (5a-8) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 33 mg of the title compound in 87% yield as off-white powder, m.p. 152-153° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.841 (s, 1H, 3-H), 6.591 (d, 1H, J=10.2 Hz, 8-H), 5.838 (d, 1H, J=10.2 Hz, 7-H), 4.763 (m, 1H, 10-H), 2.755 (dd, 1H, J=11.7 Hz, 16.5 Hz, 11-He), 2.657 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.462 (d, 3H, J=6.0 Hz, 10-CH₃), 1.441, 1.408 (2s, 6H, CH₃);

ESI-MS (m/z): 381.1 [M+H]⁺ (MW=380.32)

Elemental analysis: Calculated for C₁₉H₁₅F₃O₅ (%): C, 60.00; H, 3.98. Found (%): C, 59.99; H, 4.18.

Example 9 6,6,10-trimethyl-4-ethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-9, R₁═CH₂CH₃, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-ethyl-5,7-dihydroxy-coumarin (6-9, R₁═CH₂CH₃, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 6.63 g (0.046 mol) ethyl propionylacetate as starting material to obtain 9.2 g of the title compound in 97% yield as a yellowish powder crystalline. m.p. 241-243° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.556 (s, 1H, 7-OH), 10.266 (s, 1H, 5-OH), 6.264 (d, 1H, J=2.4 Hz, 8-H), 6.169 (d, 1H, J=2.4 Hz, 6-H), 5.822 (s, 1H, 3-H), 2.899 (q, 2H, J=7.2 Hz, 4-CH ₂—CH₃), 1.152 (t, 3H, J=7.2 Hz, 4-CH₂—CH ₃);

ESI-MS (m/z): 207.1 [M+H]⁺ (MW=206.20);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-8-methyl-2,10-dione (5a-9, R₁=CH₂CH₃, R₂═R₄═H, R₃═CH₃) and benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-8-methyl-2,6-dione (5b-9, R₁═CH₂CH₃, R₂═R₄═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.06 g (10 mmol) 4-ethyl-5,7-dihydroxy-coumarin (6-9) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.1 g of the title compound 5a-9 in 77% yield as a white powder (m.p. 165-166° C.) and 0.52 g of the title compound 5b-9 in 19% yield as a white powder (m.p. 192-193° C.).

Compound 5a-9: ¹HNMR (300 MHz, DMSO-d₆, ppm): 6.291 (s, 1H, 6-H), 6.036 (s, 1H, 3-H), 4.637 (m, 1H, 8-H), 2.932 (q, 2H, J=7.2 Hz, 4-CH ₂CH₃), 2.651 (dd, 1H, J=11.4 Hz, 16.5 Hz, 9-He), 2.564 (dd, 1H, J=3.9 Hz, 16.5 Hz, 9-Ha), 1.386 (d, 3H, J=6.0 Hz, 8-CH₃), 1.150 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 275.1 [M+H]⁺ (MW=274.27);

Elemental analysis: Calculated for C₁₅H₄O₅.2H₂O (%): C, 58.06; H, 5.84. Found (%): C, 58.33; H, 5.74.

Compound 5b-9: ¹H-NMR (400 MHz, DMSO-d₆, ppm): 13.904 (s, 1H, 5-OH), 6.462 (s, 1H, 10-H), 6.051 (s, 1H, 3-H), 4.743 (m, 1H, 8-H), 2.933 (m, 2H, 7-CH₂), 2.816 (q, 2H, J=6.2 Hz, 4-CH ₂CH₃), 1.434 (d, 3H, J=4.8 Hz, 8-CH₃), 1.176 (t, 3H, J=6.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 275.1 [M+H]⁺ (MW=274.27);

Elemental analysis: Calculated for C₁₅H₁₄O₅ (%): C, 6.69; H, 5.15. Found (%): C, 65.60; H, 5.17.

(3) 6,6,10-trimethyl-4-ethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-9, R₁═CH₂CH₃, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 27 mg (0.1 mmol) benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-2,10-dione (5a-9) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 28 mg of the title compound in 84% yield as off-white powder, m.p. 133-135° C.

¹H-NMR (400 MHz, DMSO-d₆): 6.593 (d, 1H, J=10.0 Hz, 8-H), 6.116 (s, 1H, 3-H), 5.796 (d, 1H, J=10.0 Hz, 7-H), 4.716 (m, 1H, 10-H), 2.935 (q, 2H, J=7.2 Hz, 4-CH ₂CH₃), 2.723 (dd, 1H, J=11.6 Hz, 16.4 Hz, 11-He), 2.627 (dd, 1H, J=3.6 Hz, 16.4 Hz, 11-Ha), 1.504, 1.468 (2s, 6H, 6-CH₃), 1.447 (d, 3H, J=6.0 Hz, 10-CH₃), 1.182 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 341.1 [M+H]⁺ (MW=340.38);

Elemental analysis: Calculated for C₂₀H₂₀O₅.1/2H₂O (%): C, 68.75; H, 6.05. Found (%): C, 68.67; H, 5.78.

Example 10 6,6,10-trimethyl-4-ethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-10, R₁═CH₂CH₃, R₂═F, R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-ethyl-3-fluoro-5,7-dihydroxy-coumarin (6-10, R₁═CH₂CH₃, R₂═F)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 7.5 g (0.046 mol) Ethyl 2-fluoro propionylacetate as starting material to obtain 9.5 g of the title compound in 92% yield as a yellowish powder crystalline. m.p. 227-229° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.643 (s, 1H, OH), 10.286 (s, 1H, OH), 6.330 (d, 1H, J=2.4 Hz, 8-H), 6.219 (d, 1H, J=2.4 Hz, 6-H), 2.981 (dq, 2H, J=3.3 Hz, 7.2 Hz, 4-CH ₂CH₃), 1.177 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 225.1 [M+H]⁺ (MW=224.18);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-3-fluoro-8-methyl-2,10-dione (5a-10, R₁═CH₂CH₃, R₂═F, R₄═H, R₃═CH₃) and benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-3-fluoro-8-methyl-2,6-dione (5b-10, R₁=CH₂CH₃, R₂═F, R₄═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.24 g (10 mmol) 4-ethyl-3-fluoro-5,7-dihydroxy-coumarin (6-10) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 1.9 g of the title compound 5a-10 in 65% yield as a yellowish powder (m.p. 138-141° C.) and 0.23 g of the title compound 5b-10 in 8% yield as a yellowish powder (m.p. 151-152° C.).

Compound 5a-10: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 11.872 (s, 1H, OH), 6.349 (s, 1H, 6-H), 4.637 (m, 1H, 8-H), 2.982 (q, 2H, J=7.5 Hz, 4-CH ₂CH₃), 2.664 (dd, 1H, J=11.1 Hz, 16.5 Hz, 9-He), 2.596 (dd, 1H, J=3.3 Hz, 16.5 Hz, 9-Ha), 1.390 (d, 3H, J=6.3 Hz, 8-CH₃), 1.168 (t, 3H, J=7.5 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 293.1 [M+H]⁺ (MW=292.27);

Elemental analysis: Calculated for C₁₅H₁₃FO₅.1/4H₂O (%): C, 60.71; H, 4.58. Found (%): C, 60.66; H, 4.44.

Compound 5b-10: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 13.819 (s, 1H, OH), 6.537 (s, 1H, 10-H), 4.750 (m, 1H, 8-H), 2.990 (q, 2H, J=7.5 Hz, 4-CH ₂CH₃), 2.965 (dd, 1H, J=12.0 Hz, 17.7 Hz, 7-He), 2.808 (dd, 1H, J=3.3 Hz, 17.7 Hz, 7-Ha), 1.440 (d, 3H, J=6.3 Hz, 8-CH₃), 1.201 (t, 3H, J=7.5 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 293.1 [M+H]⁺ (MW=292.27)

(3) 6,6,10-trimethyl-4-ethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-10, R₁═CH₂CH₃, R₂═F, R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-3-fluoro-8-methyl-2,10-dione (5a-10) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 30 mg of the title compound in 85% yield as off-white powder, m.p. 142-144° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.588 (d, 1H, J=10.2 Hz, 8-H), 5.821 (d, 1H, J=10.2 Hz, 7-H), 4.712 (m, 1H, 10-H), 2.972 (dq, 2H, J=7.2 Hz, 3.6 Hz, 4-CH ₂CH₃), 2.725 (dd, 1H, J=11.7 Hz, 16.8 Hz, 11-He), 2.629 (dd, 1H, J=3.6 Hz, 16.8 Hz, 11-Ha), 1.505, 1.470 (2s, 6H, CH₃), 1.448 (d, 3H, J=6.3 Hz, 10-CH₃), 1.200 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 359.2 [M+H]⁺ (MW=358.37);

Elemental analysis: Calculated for C₂₀H₁₉FO₅.1/5H₂O (%): C, 66.36; H, 5.40. Found (%): C, 66.40; H, 5.44.

Example 11 6,6,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-11, R₁=n-C₃H₇, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-n-propyl-5,7-dihydroxy-coumarin (6-11, R₁=n-C₃H₇)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 7.3 g (0.046 mol) ethyl butyrylacetate as starting material to obtain 9.4 g of the title compound in 93% yield as a yellowish powder crystalline. m.p. 229-231° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.558 (s, 1H, OH), 10.270 (s, 1H, OH), 6.256 (d, 1H, J=2.4 Hz, 8-H), 6.166 (d, 1H, J=2.4 Hz, 6-H), 5.798 (s, 1H, 3-H), 2.824 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 1.557 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 0.917 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 221.1 [M+H]⁺ (MW=220.23)

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-methyl-2,10-dione (5a-11, R₁=n-C₃H₇, R₂═R₄═H, R₃═R₅═R₆═CH₃) and benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-methyl-2,6-dione (5b-11, R₁=n-C₃H₇, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.24 g (10 mmol) 4-n-propyl-5,7-dihydroxy-coumarin (6-11) and 0.92 g (10.7 mmol) of crotonic acid as starting material to obtain 2.0 g of the title compound 5a-11 in 70% yield as a white powder (m.p. 137-138° C.) and 0.26 g of the title compound 5b-11 in 9% yield as a white powder (m.p. 161-162° C.).

Compound 5a-11: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 11.760 (s, 1H, OH), 6.282 (s, 1H, 6-H), 6.025 (s, 1H, 3-H), 4.635 (m, 1H, 8-H), 2.863 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.648 (dd, 1H, J=11.1 Hz, 16.5 Hz, 9-He), 2.562 (dd, 1H, J=4.2 Hz, 16.5 Hz, 9-Ha), 1.552 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.385 (d, 3H, J=6.0 Hz, 8-CH₃), 0.924 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 289.1 [M+H]⁺ (MW=288.30)

Compound 5b-11: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 13.900 (s, 1H, OH), 6.450 (s, 1H, 10-H), 6.042 (s, 1H, 3-H), 4.753 (m, 1H, 8-H), 2.971 (dd, 1H, J=12.3 Hz, 17.4 Hz, 7-He), 2.875 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.793 (dd, 1H, J=3.0 Hz, 17.4 Hz, 7-Ha), 1.584 (sex, 2H, J=7 .Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.437 (d, 3H, J=6.3 Hz, 8-CH₃), 0.948 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 289.1 [M+H]⁺ (MW=288.30)

(3) 6,6,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-11, R₁=n-C₃H₇, R₂=R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-2,10-dione (5a-11) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 31 mg of the title compound in 88% yield as white powder, m.p. 133-134° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): ¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.566 (d, 1H, J=9.9 Hz, 8-H), 6.086 (s, 1H, 3-H), 5.774 (d, 1H, J=9.9 Hz, 7-H), 4.707 (m, 1H, 10-H), 2.837 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.708 (dd, 1H, J=12.0 Hz, 16.5 Hz, 11-He), 2.606 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.537 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH₂CH₃), 1.488, 1.450 (2s, 6H, CH₃), 1.439 (d, 3H, J=6.3 Hz, 10-CH₃), 0.963 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 355.1 [M+H]⁺ (MW=354.41);

Elemental analysis: Calculated for C₂₁H₂₂O₅.1/2H₂O (%): C, 69.41; H, 6.37. Found (%): C, 69.29; H, 6.03.

Example 12 6,6,10,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-12, R₁=n-C₃H₇, R₂═R₄═H, R₃=di-CH₃, R₅═R₆═CH₃)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8,8-dimethyl-2,10-dione (5a-12, R₁=n-C₃H₇, R₃=di-CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (O₁ mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.07 g (10.7 mmol) 3,3-dimethyl-propenoic acid as starting material to obtain 2.62 g of the title compound 5a-12 in 87% yield as a white powder m.p. 162-164° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 11.755 (s, 1H, 5-OH), 6.257 (s, 1H, 6-H), 6.026 (s, 1H, 3-H), 2.861 (t, 2H, J=7.4 Hz, 4-CH ₂CH₂CH₃), 2.688 (s, 2H, 9-CH₂), 1.560 (m, 2H, J=7.4 Hz, 4-CH₂CH ₂CH₃), 1.375 (s, 6H, 8-CH₃), 0.927 (t, 3H, J=7.4 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 303.1 [M+H]⁺ (MW=302.33);

Elemental analysis: Calculated for C₁₇H₁₈O₅.1/2H₂O (%): C, 65.58; H, 6.15. Found: C, 65.69; H, 5.73.

(2) 6,6,10,10-tetramethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-12, R₁=n-C₃H₇, R₂═R₄═H, R₃=di-CH₃, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 30 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8,8-dimethyl-2,10-dione (5a-12) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 29 mg of the title compound in 80% yield as off-white powder, m.p. 110-112° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 6.585 (d, 1H, J=10.4 Hz, 8-H), 6.100 (s, 1H, 3-H), 5.783 (d, 1H, J=10.4 Hz, 7-H), 2.849 (t, 2H, J=7.6 Hz, 4-CH ₂CH₂CH₃), 2.754 (s, 2H, 11-CH₂), 1.566 (m, 2H, J=7.6 Hz, 7.4 Hz, 4-CH₂CH ₂CH₃), 1.481 (s, 6H, 6-CH₃), 1.417 (s, 6H, 10-CH₃), 0.970 (t, 3H, J=7.4 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 369.2 [M+H]⁺ (MW=368.43);

Elemental analysis: Calculated for C₂₂H₂₄O₅ (%): C, 71.72; H, 6.57. Found (%): C, 71.65; H, 6.55.

Example 13 6,6-dimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-13, R₁=n-C₃H₇, R₂═R₃═R₄═H, R₅═R₆═CH₃,)

(1) 5-hydroxyl-4-n-propyl-benzo[2,3-f]-pyranyl-2,10-dione (5a-13, R₁=n-C₃H₇, R₂═R₃═R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (10 mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.14 g (10.7 mmol) trans-3-chloro-propenoic acid as starting material to obtain 1.03 g of the title compound 5a-13 in 28% yield as a white powder, m.p. 116-118° C.

¹H-NMR (300 MHz, DMSO-d₆): 11.861 (s, 1H, 5-OH), 8.134 (d, 1H, J=9.9 Hz, 8-H), 6.841 (s, 1H, 6-H), 6.292 (d, 1H, J=9.9 Hz, 9-H), 6.174 (s, 1H, 3-H), 2.924 (t, 2H, J=7.5 Hz, 10-CH₂), 1.597 (sex, 2H, J=7.5 Hz, 7.2 Hz, 11-CH₂), 0.952 (t, 3H, J=7.2 Hz, 12-CH₃);

ESI-MS (m/z): 273.1 [M+H]⁺ (MW=272.26);

(2) 6,6-dimethyl-4-n-propyl-2H,6H,12H-benzo[2,3-f:2′,3′-h]-tripyranyl-2,12-dione

(4-13, R₁=n-C₃H₇, R₂═R₃═R₄═H, R₅═R₆═CH₃,)

Using the same procedure as described in the preparative method of compound 4-1, except for using 27 mg (0.1 mmol) 5-hydroxyl-4-n-propyl-benzo[2,3-f]-pyranyl-2,10-dione (5a-13) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 24 mg of the title compound in 71% yield as off-white powder, m.p. 102-104° C.

¹H-NMR (300 MHz, DMSO-d₆): 8.142 (d, 1H, J=9.9 Hz, 10-H), 6.692 (d, 1H, J=10.5 Hz, 8-H), 6.374 (d, 1H, J=9.9 Hz, 11-H), 6.238 (s, 1H, 3-H), 5.923 (d, 1H, J=9.9 Hz, 7-H), 2.885 (t, 2H, J=7.5 Hz, 13-CH₂), 1.591 (sex, 2H, J=7.5 Hz, 7.2 Hz, 14-CH₂), 1.505 (s, 6H, 6-CH₃), 0.993 (t, 3H, J=7.2 Hz, 15-CH₃);

ESI-MS (m/z): 339.2 [M+H]⁺ (MW=338.36);

Example 14 6,6-dimethyl-4,10-di-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-di-n-propyl-2,10-dione (5a-14, R₁═R₃=n-C₃H₇, R₂═R₄═H) and benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-di-n-propyl-2,6-dione (5b-14, R₁═R₃=n-C₃H₇, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.24 g (10 mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.22 g (10.7 mmol) trans-2-hydrosorbic acid as starting material to obtain 2.5 g of the title compound 5a-14 in 79% yield as a white powder (m.p. 121-123° C.) and 0.32 g of the title compound 5b-14 in 10% yield as a white powder (m.p. 136-138° C.).

Compound 5a-14: ¹H-NMR (300 MHz, DMSO-d₆): 11.768 (s, 1H, 5-OH), 6.284 (s, 1H, 6-H), 6.031 (s, 1H, 3-H), 4.514 (m, 1H, 8-H), 2.864 (t, 2H, J=7.5 Hz, 11-CH₂), 2.653 (dd, 1H, J=11.4 Hz, 16.5 Hz, 9-He), 2.562 (dd, 1H, J=3.9 Hz, 16.5 Hz, 9-Ha), 1.714 (m, 2H, 14-CH₂), 1.556 (sex, 2H, J=7.5 Hz, 7.2 Hz, 12-CH₂), 1.432 (m, 2H, 15-CH₂), 0.925 (t, 3H, J=7.2 Hz, 13-CH₃), 0.900 (t, 3H, J=7.2 Hz, 16-CH₃);

ESI-MS (m/z): 317.0 [M+H]⁺ (MW=316.36);

Elemental analysis: Calculated for C₁₈H₂₀O₅.1/2H₂O (%): C, 66.45; H, 6.50. Found (%): C, 66.44; H, 6.29.

Compound 5b-14: ¹H-NMR (300 MHz, DMSO-d₆): 13.876 (s, 1H, 5-OH), 6.427 (s, 1H, 10-H), 6.030 (s, 1H, 3-H), 4.626 (m, 1H, 8-H), 2.953 (dd, 1H, J=12.3 Hz, 17.4 Hz, 7-He), 2.862 (m, 2H, 11-CH₂), 2.782 (dd, 1H, J=3.3 Hz, 17.4 Hz, 7-Ha), 1.712 (m, 2H, 14-CH₂), 1.576 (sex, 2H, J=7.2 Hz, 7.5 Hz, 12-CH₂), 1.442 (m, 2H, 15-CH₂), 0.945 (t, 3H, J=7.2 Hz, 13-CH₃), 0.922 (t, 3H, J=7.2 Hz, 16-CH₃);

ESI-MS (m/z): 317.0 [M+H]⁺ (MW=316.36);

(2) 6,6-dimethyl-4,10-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-14, R₁═R₃=n-C₃H₇, R₂═R₄═H, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 32 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-di-n-propyl-2,10-dione (5a-14) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 31 mg of the title compound in 81% yield as off-white powder, m.p. 141-143° C.

¹H-NMR (300 MHz, DMSO-d₆): 6.549 (d, 1H, J=10.2 Hz, 8-H), 6.082 (s, 1H, 3-H), 5.782 (d, 1H, J=10.2 Hz, 7-H), 4.577 (o, 1H, J=3.6 Hz, 11.7 Hz, 4.2 Hz, 10-H), 2.830 (t, 2H, J=7.8 Hz, 12-CH₂), 2.704 (dd, 1H, J=11.7 Hz, 16.5 Hz, 11-He), 2.596 (dd, 1H, J=3.6 Hz, 16.2 Hz, 11-Ha), 1.766 (m, 2H, 15-CH₂), 1.673 (m, 2H, 13-CH₂), 1.561 (m, 2H, 16-CH₂), 1.490, 1.450 (2s, 6H, 6-CH₃), 0.962 (t, 3H, J=6.9 Hz, 14-CH₃), 0.934 (t, 3H, J=7.2 Hz, 17-CH₃);

ESI-MS (m/z): 383.1 [M+H]⁺ (MW=382.46);

Elemental analysis: Calculated for C₂₃H₂₆O₅.1/8H₂O (%): C, 71.80; H, 6.87. Found (%): C, 71.75; H, 6.73.

Example 15 6,6-dimethyl-4-n-propyl-10-n-pentyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-15, R₁=n-C₃H₇, R₂═R₄═H, R₃=n-C₅H₁₁, R₅═R₆═CH₃)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-n-pentyl-2,10-dione (5a-15, R₁=n-C₃H₇, R₂═R₄═H, R₃=n-C₅H₁₁)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (10 mmol) of 2.24 g (10 mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.52 g (10.7 mmol) trans-2-n-octenoic acid as starting material to obtain 2.2 g of the title compound 5a-15 in 64% yield as a yellowish powder, m.p. 146-148° C.

¹H-NMR (300 MHz, DMSO-d₆): 11.765 (s, 1H, 5-OH), 6.288 (s, 1H, 6-H), 6.036 (s, 1H, 3-H), 4.510 (m, 1H, 8-H), 2.868 (t, 2H, J=7.5 Hz, 11-CH₂), 2.657 (dd, 1H, J=11.1 Hz, 16.5 Hz, 9-He), 2.566 (dd, 1H, J=3.9 Hz, 16.5 Hz, 9-Ha), 1.707 (m, 2H, 14-CH₂), 1.558 (sex, 2H, J=7.5 Hz, 7.2 Hz, 12-CH₂), 1.416 (m, 2H, 15-CH₂), 1.283 (m, 4H,16,17-CH₂), 0.926 (t, 3H, J=7.2 Hz, 13-CH₃), 0.868 (t, 3H, J=6.9 Hz, 18-CH₃);

ESI-MS (m/z): 345.1 [M+H]⁺ (MW=344.41);

Elemental analysis: Calculated for C₂₀H₂₄O₅ (%): C, 69.75; H, 7.02. Found (%): C, 69.52; H, 6.90.

(2) 6,6-dimethyl-4-n-propyl-10-n-pentyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-15, R₁=n-C₃H₇, R₂═R₄═H, R₃=n-C₅H₁₁, R₅═R₆=CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 34 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-n-pentyl-2,10-dione (5a-15) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 33 mg of the title compound in 80% yield as off-white powder, m.p. 128-131° C.

¹H-NMR (300 MHz, DMSO-d₆): 6.558 (d, 1H, J=9.9 Hz, 8-H), 6.099 (s, 1H, 3-H), 5.800 (d, 1H, J=10.2 Hz, 7-H), 4.569 (o, 1H, J=3.9 Hz, 12.0 Hz, 4.2 Hz, 10-H), 2.845 (dt, 2H, J=3.6 Hz, 8.4 Hz, 13-CH₂), 2.717 (dd, 1H, J=12.0 Hz, 16.5 Hz, 11-He), 2.609 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.746 (m, 2H, 16-CH₂), 1.546 (sex, 2H, J=8.4 Hz, 7.2 Hz, 14-CH₂), 1.499, 1.458 (2s, 6H, 6-CH₃), 1.310 (m, 6H,17,18,19-CH₂), 0.967 (t, 3H, J=7.2 Hz, 15-CH₃), 0.871 (t, 3H, J=7.2 Hz, 20-CH₃);

ESI-MS (m/z): 411.1 [M+H]⁺ (MW=410.51);

Elemental analysis: Calculated for C₂₅H₃₀O₅.1/6H₂O (%): C, 72.62; H, 7.39. Found (%): C, 72.56; H, 7.49.

Example 16 6,6-dimethyl-4-n-propyl-10-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-16, R₁=n-C₃H₇, R₂═R₄═H, R₃═C₆H₅, R₅═R₆═CH₃)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-phenyl-2,10-dione (5a-16, R₁=n-C₃H₇, R₂═R₄═H, R₃═C₆H₅) and benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-phenyl-2,6-dione (5a-16, R₁=n-C₃H₇, R₂═R₄═H, R₃═C₆H₅)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (10 mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.59 g (10.7 mmol) trans-cinnamic acid as starting material to obtain 2.32 g of the title compound 5a-16 in 66% yield as a white powder m.p. 171-173° C., and 0.52 g of the title compound 5b-16 in 15% yield as a white powder m.p. 182-183° C.

Compound 5a-16: ¹H-NMR (300 MHz, DMSO-d₆): 11.878 (s, 1H, 5-OH), 7.445 (m, 5H, 8-Ph), 6.373 (s, 1H, 6-H), 6.066 (s, 1H, 3-H), 5.668 (dd, 1H, J=3.3 Hz, 12.6 Hz, 8-H), 3.156 (dd, 1H, J=12.3 Hz, 16.5 Hz, 9-He), 2.886 (t, 2H, J=7.2 Hz, 11-CH₂), 2.756 (dd, 1H, J=3.3 Hz, 16.5 Hz, 9-Ha), 1.572 (sex, 2H, J=7.2 Hz, 7.5 Hz, 12-CH₂), 0.936 (t, 3H, J=7.5 Hz, 13-CH₃);

ESI-MS (m/z): 351.0 [M+H]⁺ (MW=350.37);

Elemental analysis: Calculated for C₂₁H₁₈O₅.1/3H₂O (%): C, 70.77; H, 5.27. Found (%): C, 70.69; H, 4.96.

Compound 5b-16: ¹H-NMR (300 MHz, DMSO-d₆): 13.871 (s, 1H, 5-OH), 7.445 (m, 5H, 8-Ph), 6.556 (s, 1H, 10-H), 6.072 (s, 1H, 3-H), 5.768 (dd, 1H, J=3.0 Hz, 12.9 Hz, 8-H), 3.498 (dd, 1H, J=12.9 Hz, 17.4 Hz, 7-He), 2.986 (dd, 1H, J=3.0 Hz, 17.4 Hz, 7-Ha), 2.883 (dt, 2H, J=7.5 Hz, 3.3 Hz, 11-CH₂), 1.601 (sex, 2H, J=7.2 Hz, 7.5 Hz, 12-CH₂), 0.961 (t, 3H, J=7.2 Hz, 13-CH₃);

ESI-MS (m/z): 351.0 [M+H]⁺ (MW=350.37);

(2) 6,6-dimethyl-4-n-propyl-10-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-di one (4-16, R₁=n-C₃H₇, R₂═R₄═H, R₃═C₆H₅, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 35 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-phenyl-2,10-dione (5a-16) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 34 mg of the title compound in 82% yield as off-white powder, m.p. 151-153° C.

¹H-NMR (300 MHz, DMSO-d₆): 7.456 (m, 5H, 10-Ph), 6.559 (d, 1H, J=9.9 Hz, 8-H), 6.113 (s, 1H, 3-H), 5.776 (d, 1H, J=9.9 Hz, 7-H), 5.750 (dd, 1H, J=3.0 Hz, 12.3 Hz, 10-H), 3.175 (dd, 1H, J=12.3 Hz, 16.2 Hz, 11-He), 2.858 (m, 2H, 13-CH₂), 2.815 (dd, 1H, J=3.0 Hz, 16.2 Hz, 11-Ha), 1.564 (sex, 2H, J=7.2 Hz, 7.5 Hz, 14-CH₂), 1.493, 1.466 (2s, 6H, 6-CH₃), 0.970 (t, 3H, J=7.2 Hz, 15-CH₃);

ESI-MS (m/z): 417.1 [M+H]⁺ (MW=416.48);

Elemental analysis: Calculated for C₂₆H₂₄O₅.1/2 H₂O (%): C, 73.39; H, 5.92.

Found (%): C, 73.47; H, 5.61.

Example 17 6,6-dimethyl-4-n-propyl-10-p-methyl-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tri pyranyl-2,12-dione (4-17, R₁=n-C₃H₇, R₂═R₄═H, R₃=p-CH₃C₆H₄, R₅═R₆═CH₃,)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-p-methyl-phenyl-2,10-dione (5a-17, R₁=n-C₃H₇, R₂═R₄═H, R₃=p-CH₃C₆H₄)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (10 mmol) of 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.74 g (10.7 mmol) of trans-p-methylphenyl propenoic acid as starting material to obtain 2.48 g of the title compound 5a-17 in 68% yield as a white powder, m.p. 169-171° C.

¹H-NMR (300 MHz, DMSO-d₆): 11.176 (s, 1H, 5-OH), 7.094 (d, 2H, J=8.1 Hz, 8-Ar—H), 6.968 (d, 2H, J=8.1 Hz, 8-Ar—H), 6.578 (s, 1H, 6-H), 6.037 (s, 1H, 3-H), 4.665 (d, 1H, J=6.0 Hz, 8-H), 3.336 (q, 2H, J=7.2 Hz, 16.2 Hz, 9-CH₂), 2.906 (m, 2H, 11-CH₂), 2.219 (s, 3H, 14-CH₃), 1.598 (sex, 2H, J=7.2 Hz, 7.5 Hz, 12-CH₂), 0.938 (t, 3H, J=7.2 Hz, 13-CH₃);

ESI-MS (m/z): 365.1 [M+H]⁺ (MW=364.40);

Elemental analysis: Calculated for C₂₂H₂₀O₅ (%): C, 72.52; H, 5.53. Found (%): C, 72.47; H, 5.43.

(2) 6,6-dimethyl-4-n-propyl-10-p-methyl-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-17, R₁=n-C₃H₇, R₂═R₄═H, R₃=p-CH₃C₆H₄, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 36 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-p-methyl-phenyl-2,10-dione (5a-17) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 36 mg of the title compound in 85% yield as off-white powder, m.p. 174-176° C.

¹H-NMR (300 MHz, DMSO-d₆): 7.105 (d, 2H, J=7.8 Hz, 10-Ar—H), 6.991 (d, 2H, J=8.1 Hz, 10-Ar—H), 6.123 (s, 1H, 3-H), 6.622 (d, 1H, J=9.9 Hz, 8-H), 5.889 (d, 1H, J=9.9 Hz, 7-H), 4.703 (d, 1H, J=6.0 Hz, 10-H), 3.377 (dd, 2H, J=7.2 Hz, 16.2 Hz, 11-CH₂), 2.886 (m, 2H, 13-CH₂), 2.226 (s, 3H, 16-CH₃), 1.596 (sex, 2H, J=7.2 Hz, 7.5 Hz, 14-CH₂), 1.513, 1.489 (2s, 6H, 6-CH₃), 0.986 (t, 3H, J=7.2 Hz, 15-CH₃);

ESI-MS (m/z): 431.1 [M+H]⁺ (MW=430.51);

Elemental analysis: Calculated for C₂₇H₂₆O₅.1/8H₂O (%): C, 74.94; H, 6.11. Found (%): C, 75.02; H, 6.14.

Example 18 6,6-dimethyl-4-n-propyl-10,11-trans-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-18, R₁=n-C₃H₇, R₂═H, R₃,R₄=trans-cyclohexyl, R₅═R₆═CH₃)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8,9-trans-cyclohexyl-2,10-dione (5a-18, R₁=n-C₃H₇, R₃, R₄=trans-cyclohexyl, R₂═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (10 mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.35 g (10.7 mmol) trans-cyclohexenoic acid as starting material to obtain 1.38 g of the title compound 5a-18 in 42% yield as a white powder, m.p. 160-163° C.

¹H-NMR (300 MHz, DMSO-d₆): 11.781 (s, 1H, 5-OH), 6.283 (s, 1H, 6-11), 6.032 (s, 1H, 3-H), 4.162 (dt, 1H, J=4.5 Hz, 11.4 Hz, 8-H), 2.865 (t, 2H, J=7.5 Hz, 11-CH₂), 2.485 (m, 1H, 9-H), 2.114 (m, 2H, 14-CH₂), 1.721 (m, 2H, 17-CH₂), 1.544 (m, 6H, 12,15,16-CH₂), 0.924 (t, 3H, J=7.2 Hz, 13-CH₃);

ESI-MS (m/z): 329.1 [M+H]⁺ (MW=328.37);

(2) 6,6-dimethyl-4-n-propyl-10,11-trans-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-18, R₁=n-C₃H₇, R₂═H, R₃,R₄=trans-cyclohexyl, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 33 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8,9-trans-cyclohexyl-2,10-dione (5a-18) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 32 mg of the title compound in 80% yield as white powder, m.p. 151-153° C.

¹H-NMR (300 MHz, DMSO-d₆): 6.577 (d, 1H, J=10.2 Hz, 8-H), 6.104 (s, 1H, 3-H), 5.592 (d, 1H, J=9.9 Hz, 7-H), 4.238 (dt, 1H, J=4.5 Hz, 11.4 Hz, 10-H), 2.853 (dt, 2H, J=3.6 Hz, 8.4 Hz, 13-CH₂), 2.561 (m, 1H, 1H), 2.169 (m, 2H, 16-CH₂), 1.710 (m, 2H, 19-CH₂), 1.580 (m, 6H,14,17,18-CH₂), 1.503, 1.458 (2s, 6H, 6-CH₃), 0.972 (t, 3H, J=7.2 Hz, 15-CH₃);

ESI-MS (m/z): 395.1 [M+H]⁺ (MW=394.47);

Elemental analysis: Calculated for C₂₄H₂₆O₅.2/3H₂O (%): C, 70.92; H, 6.78. Found (%): C, 71.10; H, 6.79.

Example 19 6,6-dimethyl-4-n-propyl-10,11-cis-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-19, R₁=n-C₃H₇, R₂═H, R₃,R₄=cis-cyclohexyl, R₅═R₆═CH₃)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8,9-cis-cyclohexyl-2,10-dione (5a-19, R₁=n-C₃H₇, R₃, R₄=cis-cyclohexyl, R₂═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (10 mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 1.35 g (10.7 mmol) cyclohexenoic acid as starting material to obtain 1.42 g of the title compound 5a-19 in 43% yield as a white powder, m.p. 159-161° C.;

¹H-NMR (300 MHz, DMSO-d₆): 11.818 (s, 1H, 5-OH), 6.307 (s, 1H, 6-H), 6.021 (s, 1H, 3-H), 4.642 (m, 1H, 8-H), 2.860 (t, 2H, J=7.5 Hz, 11-CH₂), 2.502 (m, 2H, 14-CH₂), 1.922 (m, 1H, 9-H), 1.566 (m, 8H,12,15,16,17-CH₂), 0.923 (t, 3H, J=7.2 Hz, 13-CH₃);

ESI-MS (m/z): 329.1 [M+H]⁺ (MW=328.37);

Elemental analysis: Calculated for C₁₉H₂₀O₅ (%): C, 69.50; H, 6.14. Found (%): C, 69.44; H, 5.88.

(2) 6,6-dimethyl-4-n-propyl-10,11-cis-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-19, R₁=n-C₃H₇, R₂═H, R₃,R₄=cis-cyclohexyl, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 33 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8,9-cis-cyclohexyl-2,10-dione (5a-19) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 33 mg of the title compound in 84% yield as off-white powder, m.p. 156-159° C.

¹H-NMR (300 MHz, DMSO-d₆): 6.622 (d, 1H, J=9.9 Hz, 8-H), 6.095 (s, 1H, 3-H), 5.785 (d, 1H, J=10.2 Hz, 7-H), 4.727 (m, 1H, 10-H), 2.843 (t, 2H, J=7.5 Hz, 13-CH₂), 2.544 (m, 1H, 1H), 2.166 (m, 2H, 16-CH₂), 1.573 (m, 6H,14,17,18-CH₂), 1.722 (m, 2H, 19-CH₂), 1.488, 1.479 (2s, 6H, 6-CH₃), 0.965 (t, 3H, J=7.2 Hz, 15-CH₃);

ESI-MS (m/z): 395.1 [M+H]⁺ (MW=394.47);

Elemental analysis: Calculated for C₂₄H₂₆O₅.1/6H₂O (%): C, 72.52; H, 6.68. Found (%): C, 72.46; H, 6.80

Example 20 6,6,10-trimethyl-3-chrolo-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-20, R₁=n-C₃H₇, R₂═Cl, R₃═R₅═R₆═CH₃, R₄═H)

(1) 3-chloro-4-n-propyl-5,7-dihydroxy-coumarin (6-20, R₁=n-C₃H₇, R₂═Cl)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 8.86 g (0.046 mol) 2-chloroethyl butyryl acetate as starting material to obtain 10.6 g of the title compound in 90% yield as a yellow powder crystalline. m.p. 242-245° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.811 (s, 1H, 7-OH), 10.434 (s, 1H, 5-OH), 6.307 (d, 1H, J=2.4 Hz, 8-H), 6.197 (d, 1H, J=2.4 Hz, 6-H), 3.135 (m, 2H, 4-CH ₂—C₂H₅), 1.559 (m, 2H, 4-CH₂—CH ₂—CH₃), 0.976 (t, 3H, J=7.2 Hz, 4-CH₂—CH₂—CH ₃);

ESI-MS (m/z): 255.1 [M+H]⁺ (MW=254.67);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-chloro-4-n-propyl-2,10-dione (5a-20, R₁=n-C₃H₇, R₂═Cl, R₃═CH₃, R₄═H) and benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-chloro-4-n-propyl-2,6-dione (5b-20, R₁=n-C₃H₇, R₂═Cl, R₃═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.55 g (10 mmol) 3-chloro-4-n-propyl-5,7-dihydroxy-coumarin (6-20) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.4 g of the title compound 5a-20 in 75% yield as a white powder, m.p. 164-165° C., and 0.30 g of the title compound 5b-20 in 9.3% yield as a white powder m.p. 188-189° C.

Compound 5a-20: ¹HNMR (300 MHz, DMSO-d₆, ppm): 12.016 (s, 1H, OH), 6.345 (s, 1H, 6-H), 4.657 (m, 1H, 8-H), 3.155 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.658 (dt, 2H, J=3.3 Hz, 11.1 Hz, 9-CH₂), 1.558 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.392 (d, 3H, J=6.0 Hz, 8-CH₃), 0.985 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 323.1 [M](MW=322.75);

Elemental analysis: Calculated for C₁₆H₁₅ClO₅ (%): C, 59.54; H, 4.68. Found (%): C, 59.44; H, 4.69.

Compound 5b-20: ¹H-NMR (400 MHz, DMSO-d₆, ppm): 14.134 (s, 1H, 5-OH), 6.531 (s, 1H, 10-H), 4.774 (dq, 1H, J=6.4 Hz, 3.2 Hz, 12.4 Hz, 8-H), 3.154 (m, 2H, 4-CH ₂CH₂CH₃), 3.002 (dd, 1H, J=12.4 Hz, 17.6 Hz, 7-He), 2.822 (dd, 1H, J=3.2 Hz, 17.2He, 7-Ha), 1.595 (dt, 1H, J=7.2 Hz, 8.0 Hz, 4-CH₂CH ₂CH₃), 1.442 (d, 3H, J=6.41 Hz, 8-CH₃), 1.016 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 323.1 [M](MW=322.75);

(3) 6,6,10-trimethyl-3-chrolo-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-20, R₁=n-C₃H₇, R₂═C₁, R₃═R₅═R₆═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 32 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-chloro-4-n-propyl-2,10-dione (5a-20) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 33 mg of the title compound in 85% yield as off-white powder, m.p. 112-114° C.

¹H-NMR (400 MHz, DMSO-d₆): 6.607 (d, 1H, J=10.0 Hz, 8-H), 5.833 (d, 1H, J=10.0 Hz, 7-H), 4.734 (m, 1H, 10-H), 3.122 (t, 2H, J=8.0 Hz, 4-CH ₂CH₂CH₃), 2.737 (dd, 1H, J=12.0 Hz, 16.4 Hz, 11-He), 2.645 (dd, 1H, J=3.6 Hz, 16.4 Hz, 11-Ha), 1.581 (m, 2H, 4-CH₂CH ₂CH₃), 1.520, 1.480 (2s, 6H, 6-CH₃), 1.452 (d, 3H, J=6.0 Hz, 10-CH₃), 1.045 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 389.1 [M+H]⁺ (MW=388.85);

Elemental analysis: Calculated for C₂₁H₂₁ClO₅.1/4H₂O (%): C, 64.12; H, 5.64. Found (%): C, 64.09; H, 5.82.

Example 21 6,6,10-trimethyl-4-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-21, R₁═C₆H₅, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-phenyl-5,7-dihydroxy-coumarin (6-21, R₁═C₆H₅, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) pholoroglucinol and 8.84 g (0.046 mol) ethyl benzyl acetate as starting material to obtain 11.5 g of the title compound in 98% yield as a yellow powder crystalline. m.p. 226-228 C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.371 (s, 1H, 7-OH,), 10.085 (s, 1H, 5-OH,), 7.334 (m, 5H, 4-Ph), 6.253 (d, 1H, J=2.1 Hz, 8-H), 6.147 (d, 1H, J=2.1 Hz, 6-H), 5.729 (s, 1H, 3-H);

ESI-MS (m/z): 255.2 [M+H]⁺ (MW=254.24)

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-phenyl-2,10-dione (5a-21, R₁═C₆H₅, R₂═R₄═H, R₃═CH₃) and benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-phenyl-2,6-dione (5b-21, R₁═C₆H₅, R₂═R₄═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.55 g (10 mmol) 4-phenyl-5,7-dihydroxy-coumarin (6-21) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 1.74 g of the title compound 5a-21 in 54% yield as a white powder m.p. 126-129 L, and 0.39 g of the title compound 5b-21 in 12% yield as a white powder m.p. 151-154° C.

Compound 5a-21: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 11.327 (s, 1H, 5-OH,), 7.319 (m, 5H, 4-Ph), 6.161 (s, 1H, 6-H), 5.960 (s, 1H, 3-H), 4.666 (m, 1H, 8-H), 2.630 (m, 2H, 9-CH₂), 1.396 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 323.1 [M+H]⁺ (MW=322.32);

IR (KBr, cm⁻¹): 3059, 2970, 2725, 1745, 1610, 1550, 1367, 1242, 1147, 854, 825;

Elemental analysis: Calculated for C₁₉H₁₄O₅ (%): C, 70.80; H, 4.38. Found (%): C, 70.98; H, 4.66.

Compound 5b-21: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 13.273 (s, 1H, 5-OH,), 7.400 (m, 5H, 4-Ph), 6.536 (s, 1H, 10-H), 5.967 (s, 1H, 3-H), 4.738 (m, 1H, 8-H), 2.921 (dd, 1H, J=17.4 Hz, 12.2 Hz, 7-He), 2.748 (dd, 1H, J=17.4 Hz, 3.3 Hz, 7-Ha), 1.429 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 323.1 [M+H]⁺ (MW=322.32);

Elemental analysis: Calculated for C₁₉H₁₄O₅.1/2H₂O (%): C, 68.87; H, 4.56. found (%): C, 68.73; H, 4.66

(3) 6,6,10-trimethyl-4-phenyl2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-21, R₁═C₆H₅, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 32 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-phenyl-2,10-dione (5a-21) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 32 mg of the title compound in 83% yield as white powder, m.p. 141-144° C.

¹H-NMR (300 MHz, CDCl₃, ppm): 7.270 (m, 5H, 4-Ph), 6.556 (d, 1H, J=9.9 Hz, 8-H), 6.063 (s, 1H, 3-H), 5.429 (d, 1H, J=9.9 Hz, 7-H), 4.667 (m, 1H, 10-H), 2.717 (m, 2H, 11-CH₂), 1.549 (d, 3H, J=6.0 Hz, 10-CH₃), 0.987, 0.944 (2s, 6H, 6-CH₃);

ESI-MS (m/z): 389.4 [M+H]⁺ (MW=388.42);

Elemental: Calculated for C₂₄H₂₀O₅ (%): C, 74.21; H, 5.19. Found (%): C, 74.40; H, 5.22.

Example 22 6,6,10-trimethyl-4-p-nitrophenyll-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-22, R₁=p-NO₂C₆H₄, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-p-nitrophenyl-5,7-dihydroxy-coumarin (6-22, R₁=p-NO₂C₆H₄, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 10.91 g (0.046 mol) p-nitrobenzoyl acetic ester as starting material to obtain 10.5 g of the title compound in 76% yield as a yellow powder crystalline. m.p. 268-270° C.

¹H-NMR (300 MHz, DMSO-d₆): 10.494 (s, 1H, OH), 10.289 (s, 1H, OH), 8.222 (d, 2H, J=9.0 Hz, Ar—H), 7.615 (d, 2H, J=9.0 Hz, Ar—H), 6.279 (d, 2H, J=2.1 Hz, 8-H), 6.151 (d, 2H, J=2.1 Hz, 6-H), 5.844 (s, 1H, 3-H);

ESI-MS (m/z): 298.1 [M−H]⁻ (MW=299.24)

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-p-nitrophenyl-2,10-dione (5a-22, R₁=p-NO₂C₆H₄, R₃═CH₃, R₂═R₄═H) or benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-p-nitrophenyl-2,6-dione (5b-22, R=p-NO₂C₆H₄, R₃═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.99 g (10 mmol) of 4-p-nitrophenyl-5,7-dihydroxy-coumarin (6-22) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.1 g of the title compound 5a-22 in 57% yield as a white powder m.p. 207-209° C., and 0.68 g of the title compound 5b-22 in 18% yield as a white powder m.p. 196-198° C.

Compound 5a-22: ¹HNMR (300 MHz, DMSO-d₆, ppm): 11.489 (s, 1H, OH), 8.238 (d, 2H, J=8.7 Hz, Ar—H), 7.616 (dd, 2H, J=2.1 Hz, 8.7 Hz, Ar—H), 6.117 (s, 1H, 6-H), 6.090 (s, 1H, 3-H), 4.667 (m, 1H, 8-H), 2.691 (dt, 2H, J=4.2 Hz, 10.5 Hz, 9-CH₂), 1.406 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 366.2 [M−H]⁻ (MW=367.32);

Elemental analysis: Calculated for C₁₉H₁₃NO₇ (%): C, 62.13; H, 3.57; N, 3.81. Found (%): C, 61.98; H, 3.75; N, 3.93.

Compound 5b-22: ¹H-NMR (300 MHz, DMSO-d₆): 13.267 (s, 1H, OH), 8.273 (m, 2H, 4-Ar—H), 7.652 (m, 2H, 4-Ar—H), 6.608 (s, 1H, 10-H), 6.126 (s, 1H, 3-H), 4.769 (m, 1H, 8-H), 2.953 (dd, 1H, J=12.3 Hz, 17.7 Hz, 7-He), 2.771 (dd, 1H, J=3.3 Hz, 17.4 Hz, 7-Ha), 1.444 (d, 3H, J=6.3 Hz, 8-CH₃);

ESI-MS (m/z): 366.2 [M−H]⁻ (MW=367.32);

(3) 6,6,10-trimethyl-4-p-nitrophenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-22, R₁=p-NO₂C₆H₄, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 37 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-p-nitrophenyl-2,10-dione (5a-22) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 32 mg of the title compound in 75% yield as white powder, m.p. 165-167° C.

¹H-NMR (300 MHz, DMSO-d₆): 8.284 (m, 2H, 4-Ar—H), 7.621 (m, 2H, 4-Ar—H), 6.509 (d, 1H, J=9.9 Hz, 8-H), 6.123 (s, 1H, 3-H), 5.613 (d, 1H, J=9.9 Hz, 7-H), 4.743 (m, 1H, 10-H), 2.754 (dd, 1H, J=11.4 Hz, 16.5 Hz, 11-He), 2.691 (dd, 1H, J=3.6 Hz, 16.5 Hz, 11-Ha), 1.458 (d, 3H, J=6.0 Hz, 10-CH₃), 0.926, 0.875 (2s, 6H, 6-CH₃);

ESI-MS (m/z): 434.2 [M+H]⁺ (MW=433.42);

Elemental analysis: Calculated for C₂₄H₁₉NO₇ (%): C, 66.51; H, 4.42; N, 3.23. Found (%): C, 66.35; H, 4.28; N, 3.26.

Example 23 6,6,10-trimethyl-4-p-aminophenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-di one (4-23, R₁=p-NH₂C₆H₄, R₂═R₄═H, R₃═R₅═R₆═CH₃)

10 ml concentrated hydrochloric acid and 0.19 g SnCl₂ (1 mmol) was added into the solution of 22 mg (0.05 mmol) 6,6,10-trimethyl-4-p-nitrophenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-22) in 10 ml EtOH. The reaction mixture was stirred in oil-bath for 2 hours at 60° C. and then cooled to room temperature, poured into the solution of 40% NaOH in protion with stirring. After extraction with dichloromethane (DCM), concentrated under reduce pressure, dried with dry NaSO₄ and purification by silica-gel column chromatography, 13 mg of the title compound 4-23 was obtained as off-white powder in 63% yield, m.p. 149-151° C.

¹H-NMR (400 MHz, DMSO-d₆): 7.089 (m, 2H, 4-Ar—H), 6.492 (m, 2H, 4-Ar—H), 6.477 (d, 1H, J=10.0 Hz, 8-H), 6.275 (d, 1H, J=8.4 Hz, 3-H), 5.577 (d, 1H, J=10.0 Hz, 7-H), 5.495 (d, 2H, J=6.0 Hz, NH₂), 4.647 (m, 1H, 10-H), 2.840 (dd, 1H, J=12.4 Hz, 15.6 Hz, 11-He), 2.677 (dd, 1H, J=3.2 Hz, 15.6 Hz, 11-Ha), 1.453 (d, 3H, J=6.0 Hz, 10-CH₃), 1.273, 1.224 (2s, 6H, 6-CH₃);

ESI-MS (m/z): 404.1 [M+H]⁺ (MW=403.44);

HRESIMS: Calculated for C₂₄H₂₂NO₅ ⁺ (m/z): 404.14979. found (m/z): 404.1495.

Example 24 6,6,10-trimethyl-4-(3,4,5-trimethoxyl)-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-24, R₁=(3,4,5-trimethoxyl)-phenyl, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-(3,4,5-trimethoxyl)-phenyl-5,7-dihydroxy-coumarin (6-24, R₁=(3,4,5-trimethoxyl)-phenyl, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 12.98 g (0.046 mol) 3,4,5-trimethoxy-benzoyl acetic ester as starting material to obtain 14.9 g of the title compound in 97% yield as a white powder crystalline. m.p. 218-220° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.368 (s, 1H, 7-OH), 10.127 (s, 1H, 5-OH), 6.624 (s, 2H, 4-Ph), 6.248 (d, 1H, J=2.4 Hz, 8-H), 6.159 (d, 1H, J=2.4 Hz, 6-H), 5.827 (s, 1H, 3-H), 3.756 (s, 6H, —OCH₃), 3.692 (s, 3H, —OCH₃);

ESI-MS (m/z): 345.1 [M+H]⁺ (MW=344.32);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-(3,4,5-trimethoxyl)-phenyl-2,10-dione (5a-24, R₁=(3,4,5-trimethoxyl)-phenyl, R₃═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 3.44 g (10 mmol) 4-(3,4,5-trimethoxyl)-phenyl-5,7-dihydroxy-coumarin (6-24) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 1.9 g of the title compound 5a-24 in 46% yield as a white powder m.p. 178-180° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 11.363 (s, 1H, 5-OH), 6.624 (s, 2H, 4-Ar—H), 6.181 (s, 1H, 6-H), 6.061 (s, 1H, 3-H), 4.641 (m, 1H, 8-H), 3.753 (s, 6H, OCH₃), 3.679 (s, 311, OCH₃), 2.641 (m, 2H, 9-CH₂), 1.404 (d, 3H, J=6.0 Hz, 8-CH₃);

ESI-MS (m/z): 413.1 [M+H]⁺ (MW=412.40);

Elemental analysis: Calculated for C₂₂H₂₀O₅ (%): C, 64.07; H, 4.89. Found (%): C, 64.23; H, 4.47.

(3) 6,6,10-trimethyl-4-(3,4,5-trimethoxyl)-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-24, R₁=(3,4,5-trimethoxyl)-phenyl, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 41 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-(3,4,5-trimethoxyl)-phenyl-2,10-dione (5a-24- and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 37 mg of the title compound in 77% yield as white powder, m.p. 129-131° C.

¹H-NMR (400 MHz, DMSO-d₆): 6.622 (s, 2H, 4-Ar—H), 6.512 (d, 1H, J=10.0 Hz, 8-H), 6.072 (s, 1H, 3-H), 5.625 (d, 1H, J=10.0 Hz, 7-H), 4.729 (m, 1H, 10-H), 3.741 (s, 6H, OCH₃), 3.689 (s, 3H, OCH₃), 2.691 (m, 2H, 11-CH₂), 1.493, 1.459 (2s, 6H, 6-CH₃), 1.453 (d, 3H, J=5.2 Hz, 10-CH₃);

ESI-MS (m/z): 479.1 [M+H]⁺ (MW=478.50);

Elemental analysis: Calculated for C₂₇H₂₆O₈.H₂O (%): C, 65.31; H, 5.68. Found (%): C, 65.09; H, 5.92.

Example 25 6,6,10-trimethyl-4-(3-(2,6-dichloro-5-fluoro)pyridinyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-25, R₁=3-(2,6-dichloro-5-fluoro)pyridinyl, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-(3-(2,6-dichloro-5-fluoro)pyridinyl)-5,7-dihydroxy-coumarin (6-25, R₁=3-(2,6-dichloro-5-fluoro)pyridinyl, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 12.88 g (0.046 mol) 3-(2,6-dichloro-5-fluoro)pyridinyl acetic ester as starting material to obtain 15.1 g of the title compound in 96% yield as a yellowish powder crystalline. m.p. >300° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.535 (s, 1H, 7-OH), 10.473 (s, 1H, 5-OH), 8.215 (d, 1H, J=8.0 Hz, 4-Ar—H), 6.284 (d, 1H, J=1.6 Hz, 8-H), 6.142 (d, 1H, J=1.6 Hz, 6-H), 6.041 (s, 1H, 3-H);

ESI-MS (m/z): 342.1 M⁺ (MW=342.11);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-(3-(2,6-dichloro-5-fluoro)pyridinyl)-2,10-dione (5a-25, R₁=3-(2,6-dichloro-5-fluoro)pyridinyl, R₃═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 3.42 g (10 mmol) of 4-(3-(2,6-dichloro-5-fluoro)pyridinyl)-5,7-dihydroxy-coumarin (6-25) and 0.76 g (10.7 mmol) crotonic acid as starting material to obtain 3.2 g of the title compound 5a-25 in 78% yield as a white powder, m.p. 197-199° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 11.727 (s, 1H, 5-OH), 8.219 (dd, 1H, J=1.2 Hz, 8.0 Hz, CH), 6.301 (s, 1H, 6-H), 6.181 (d, 1H, J=1.2 Hz, 3-H), 4.697 (m, 1H, 8-H), 2.685 (m, 2H, 9-CH₂), 1.395 (d, 3H, J=6.0 Hz, 8-CH₃);

ESI-MS (m/z): 410.2[M]⁺ (MW=410.18);

(3) 6,6,10-trimethyl-4-(3-(2,6-dichloro-5-fluoro)pyridinyl)-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-25, R₁=3-(2,6-dichloro-5-fluoro)pyridinyl, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 41 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-(3-(2,6-dichloro-5-fluoro)pyridinyl)-2,10-dione (5a-25) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 38 mg of the title compound in 81% yield as white powder, m.p. 158-160° C.

¹H-NMR (400 MHz, DMSO-d₆): 8.256 (dd, 1H, J=2.8 Hz, 8.4 Hz, 4-Ar—H), 6.525 (d, 1H, J=10.4 Hz, 8-H), 6.386 (s, 1H, 3-H), 5.680 (d, 1H, J=10.4 Hz, 7-H), 4.793 (m, 1H, 10-H), 2.719 (m, 2H, 11-CH₂), 1.464, 1.449 (2s, 6H, 6-CH₃), 1.451 (d, 3H, J=6.4 Hz, 10-CH₃);

ESI-MS (m/z): 476.1 (478.1) M⁺ (MW=476.29);

Elemental analysis: Calculated for C₂₃H₁₆Cl₂FNO₅ (%): C, 58.00; H, 3.39; N, 2.94. Found (%): C, 57.98; H, 3.66; N, 3.16.

Example 26 6,6,10-trimethyl-3,4-cyclopentyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-26, R₁,R₂=3,4-cyclopentyl, R₃═R₅═R₆═CH₃, R₄═H)

(1) 3,4-cyclopentyl-5,7-dihydroxy-coumarin (6-26, R₁,R₂=3,4-cyclopentyl)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 7.18 g (0.046 mol) ethyl 2-oxo-cyclopentonate as starting material to obtain 9.7 g of the title compound in 96% yield as a white powder crystalline. m.p. 216-218° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.394 (s, 1H, OH), 6.250 (d, 1H, J=2.4 Hz, 8-H), 6.180 (d, 1H, J=2.4 Hz, 6-H), 3.198 (t, 2H, J=7.8 Hz, 4-CH₂), 2.582 (t, 2H, J=7.5 Hz, 3-CH₂), 1.972 (m, 2H, J=7.5 Hz, 7.8 Hz, CH₂);

ESI-MS (m/z): 219.1 [M+H]⁺ (MW=218.21);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3,4-cyclopentyl-2,10-dione (5a-26, R₁,R₂=3,4-cyclopentyl R₃═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.18 g (10 mmol) 3,4-cyclopentyl-5,7-dihydroxy-coumarin (6-26) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.1 g of the title compound 5a-26 in 73% yield as a yellowish powder, m.p. 154-155° C.

¹HNMR (300 MHz, DMSO-d₆, ppm): 11.547 (s, 1H, OH), 6.236 (s, 1H, 6-H), 4.629 (m, 1H, 8-H), 3.228 (t, 2H, J=7.5 Hz, CH₂), 2.650 (m, 2H, 9-CH₂), 2.584 (m, 2H, CH₂), 1.989 (m, 2H, CH₂), 1.387 (d, 3H, J=6.0 Hz, 8-CH₃);

ESI-MS (m/z): 287.1 [M+H]⁺ (MW=286.28);

Elemental analysis: Calculated for C₁₆H₁₄O₅.2/3H₂O (%): C, 64.42; H, 5.18. found (%): C, 64.20; H, 5.39.

(3) 6,6,10-trimethyl-3,4-cyclopentyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-26, R₁,R₂=3,4-cyclopentyl, R₃═R₅═R₆═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1 in example 1, except for using 28 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3,4-cyclopentyl-2,10-dione (5a-26) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 25 mg of the title compound in 71% yield as white powder, m.p. 108-109° C.

¹H-NMR (400 MHz, DMSO-d₆): 6.559 (d, 1H, J=10.0 Hz, 8-H), 5.768 (d, 1H, J=10.0 Hz, 7-H), 4.713 (m, 1H, 10-H), 3.258 (m, 2H, CH₂), 2.633 (m, 2H, CH₂), 2.025 (m, 2H, CH₂), 1.472 (m, 2H, CH₂), 1.450, 1.439 (2s, 6H, 6-CH₃), 1.388 (d, 3H, J=6.4 Hz, 10-CH₃);

ESI-MS (m/z): 353.1 [M+H]⁺ (MW=352.39);

Elemental analysis: Calculated for C₂₁H₂₀O₅.4/3H₂O (%): C, 67.01; H, 6.06. Found (%): C, 66.99; H, 5.67.

Example 27 6,6,10-trimethyl-3,4-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-27, 3,4-cyclohexyl, R₃═R₅═R₆═CH₃, R₄═H)

(1) 3,4-cyclohexyl-5,7-dihydroxy-coumarin (6-27, R₁,R₂=3,4-cyclohexyl)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 7.83 g (0.046 mol) ethyl 2-oxo-cyclohexanoate as starting material to obtain 9.6 g of the title compound in 90% yield as a white powder crystalline. m.p. 224-226° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 10.336 (s, 1H, 7-OH), 10.082 (s, 1H, 5-OH), 6.239 (d, 1H, J=2.4 Hz, 8-H), 6.125 (d, 1H, J=2.4 Hz, 6-H), 3.017 (m, 2H, 4-CH₂), 2.326 (m, 2H, 3-CH₂), 1.632 (m, 4H, CH₂);

ESI-MS (m/z): 233.2 [M+H]⁺ (MW=232.23);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3,4-cyclohexyl-2,0-dione (5a-27, R₁, R₂=3,4-cyclohexyl, R₃═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.32 g (10 mmol) 3,4-cyclohexyl-5,7-dihydroxy-coumarin (6-27) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.28 g of the title compound 5a-27 in 76% yield as a yellowish powder, m.p. 149-151° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 11.493 (s, 1H, OH), 6.238 (s, 1H, 6-H), 4.611 (m, 1H, 8-H), 2.985 (br, 2H, CH₂), 2.638 (dd, 1H, J=11.4 Hz, 16.2 Hz, 9-He), 2.568 (dd, 1H, J=3.9 Hz, 16.2 Hz, 9-Ha), 2.344 (br, 2H, CH₂), 1.632 (br, 4H, CH₂), 1.378 (d, 3H, J=6.6 Hz, 8-CH₃);

ESI-MS (m/z): 301.1 [M+H]⁺ (MW=300.31);

Elemental analysis: Calculated for C₁₇H₁₆O₅.1/4H₂O (%): C, 66.99; H, 5.46. Found: C, 67.08; H, 5.60.

(3)

6,6,10-trimethyl-3,4-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-27, R₁, R₂=cyclohexyl, R₃═R₅═R₆═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 30 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3,4-cyclohexyl-2,10-dione (5a-27) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtaind 29 mg of the title compound in 79% yield as white powder, m.p. 121-123° C.

¹H-NMR (400 MHz, DMSO-d₆): 6.564 (d, 1H, J=10.0 Hz, 8-H), 5.758 (d, 1H, J=10.0 Hz, 7-H), 4.684 (m, 1H, 10-H), 3.006 (m, 2H, CH₂), 2.701 (m, 2H, 11-CH₂), 2.371 (m, 2H, CH₂), 1.653 (m, 4H, CH₂), 1.483, 1.464 (2s, 6H, 6-CH₃), 1.437 (d, 3H, J=6.8 Hz, 10-CH₃);

ESI-MS (m/z): 367.1 [M+H]⁺ (MW=366.41);

Elemental analysis: Calculated for C₂₂H₂₂O₅.H₂O (%): C, 68.73; H, 6.29. Found (%): C, 68.70; H, 6.07.

Example 28 2,10,10-trimethyl-8-n-propyl-6-thio-2,3-dihydro-6H, 10H-benzo[2,3-f:2′,3′-h]-tripyranyl-4-one (7, R₁=n-C₃H₇, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-n-propyl-5,7-di(p-methylphenylsulfonyl)-coumarin (8, R₁=n-C₃H₇, R₂═H)

2.20 g (10 mmol) 4-n-propyl-5,7-dihydroxy-coumarin (6-11) was dissolved in 20 ml pyridine and was cold in ice-water bath, then 11.44 g (60 mmol) p-methylphenylsulfonic acid chloride was added. The resulting reaction solution was stirred at room temperature overnight, then was poured into concentrated HCl/cracked ice with viorous stirring. The solid product was filtered and washed with water and then dried to obtain 4.9 g of the title compound in 93% yield as a white powder, m.p. 239-241° C.

¹H-NMR (300 MHz, DMSO-d₆): 7.762 (m, 4H,12,15-Ar—H), 7.499 (m, 4H, 13,16-Ar—H), 7.150 (d, 1H, J=2.4 Hz, 8-H), 6.781 (d, 1H, J=2.4 Hz, 6-H), 6.322 (s, 1H, 3-H), 2.691 (t, 2H, J=7.5 Hz, 9-CH₂), 2.429, 2.408 (2s, 6H,14,17-CH₃), 1.413 (sex, 2H, J=7.5 Hz, 7.2 Hz, 10-CH₂), 0.792 (t, 3H, J=7.2 Hz, 11-CH₃);

ESI-MS (m/z): 529.0 [M+H]⁺ (MW=528.60);

IR (KBr) cm⁻¹: 3087, 2962, 2877, 1743, 1612, 1421, 1379, 1194;

(2) 4-n-propyl-5,7-di(p-methylphenyl-sulfonyl)-2-thio-coumarin (9, R₁=n-C₃H₇, R₂═H)

2.64 g (5 mmol) 4-n-propyl-5,7-di(p-methylphenylsulfonyl)-coumarin (8) was dissolved in xylene and 11 g (50 mmol) P₂S₅ was added. The reaction mixture was refluxed for 12 hours and then cooled to room temperature. The excess P₂S₅ was filtered off and the filtrate was concentrated in vacuo. The residure was purified by silica gel column chromatography to afford 1.9 g of the title compound in 70% yield as yellow powder, m.p. 198-201° C.

¹H-NMR (300 MHz, DMSO-d₆): 7.768 (dd, 4H, J=8.4 Hz, 6.9 Hz, Ar—H), 7.496 (dd, 4H, J=8.1 Hz, 6.6 Hz, Ar—H), 7.345 (d, 1H, J=2.7 Hz, 8-H), 7.082 (s, 1H, 3-H), 6.859 (d, 1H, J=2.4 Hz, 6-H), 2.637 (t, 2H, J=7.5 Hz, 9-CH₂), 2.426, 2.403 (2s, 6H,14,17-CH₃), 1.403 (sex, 2H, J=7.5 Hz, 7.2 Hz, 10-CH₂), 0.785 (t, 3H, J=7.2 Hz, 11-CH₃);

ESI-MS (m/z): 545.0 [M+H]⁺ (MW=544.67);

IR (KBr) cm⁻¹: 3087, 2974, 2881, 1614, 1597, 1385, 1144.

(3) 4-n-propyl-5,7-dihydroxy-2-thio-coumarin (10, R₁=n-C₃H₇, R₂═H)

1.36 g (2.5 mmol) 4-n-propyl-5,7-di(p-methylphenyl sulfonyl)-2-thio-coumarin (9) was dissolved in 20 ml THF, 1.18 g (3.75 mmol) TBAF was added and the reaction mixture was refluxed for 10 hours and then was concentrated in vacuo. The residure was purified by silica gel column chromatography to afford 0.44 g of the title compound in 75% yield as yellow powder, m.p. 204-206° C.

¹H-NMR (300 MHz, DMSO-d₆): 10.901 (s, 1H, 7-OH), 10.634 (s, 1H, 5-OH), 6.766 (s, 1H, 3-H), 6.358 (d, 1H, J=2.4 Hz, 8-H), 6.344 (d, 1H, J=2.4 Hz, 6-H), 2.826 (t, 2H, J=7.5 Hz, 9-CH₂), 1.578 (sex, 2H, J=7.5 Hz, 7.2 Hz, 10-CH₂), 0.932 (t, 3H, J=7.2 Hz, 11-CH₃);

ESI-MS (m/z): 237.1 [M+H]⁺ (MW=236.29);

Elemental analysis: Calculated for C₁₂H₁₂O₃S (%): C, 61.00; H, 5.12. Found (%): C, 60.84; H, 5.14.

(4) 5-hydroxyl-8-methyl-4-n-propyl-2-thio-2H-benzo[2,3-f]-dipyranyl-10-one (11, R₁=n-C₃H₇, R₂═R₄═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1.

Using 118 mg (0.5 mmol) of 4-n-propyl-5,7-dihydroxy-2-thio-coumarin (10) and 43 mg (0.5 mmol) of crotonic acid as starting material to obtain 95 mg of the title compound in 63% yield as a brown yellow powder, m.p. 161-163° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 6.957 (s, 1H, 3-H), 6.365 (s, 1H, 6-H), 4.693 (m, 1H, 8-H), 2.848 (t, 2H, J=7.5 Hz, 11-CH₂), 2.696 (dd, 1H, J=11.4 Hz, 16.5 Hz, 9-He), 2.608 (dd, 1H, J=3.9 Hz, 16.5 Hz, 9-Ha), 1.564 (sex, 2H, J=7.5 Hz, 7.2 Hz, 12-CH₂), 1.406 (d, 3H, J=6.3 Hz, 8-CH₃), 0.928 (t, 3H, J=7.2 Hz, 13-CH₃);

ESI-MS (m/z): 305.1 [M+H]₊ (MW=304.37);

HRESIMS: Calculated for C₁₆H₁₇O₄S⁺ (m/z): 305.08475, found (m/z): 305.0845.

(5) 2,10,10-trimethyl-8-n-propyl-6-thio-2,3-dihydro-6H, 10H-benzo[2,3-f:2′,3′-h]-tripyran yl-4-one (7, R₁=n-C₃H₇, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 76 mg (0.25 mmol) 5-hydroxyl-8-methyl-4-n-propyl-2-thio-2H-benzo[2,3-f]-dipyranyl-10-one (11) and 158 mg (1 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 58 mg of the title compound in 63% yield as brown yellow powder, m.p. 139-141° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 7.003 (s, 1H, CH), 6.606 (d, 1H, J=9.9 Hz, CH), 5.839 (d, 1H, J=10.2 Hz, CH), 5.311 (m, 1H, CH), 2.825 (m, 21-, CH₂), 2.716 (m, 2H, CH₂), 1.580 (m, 2H, CH₂), 1.516, 1.478 (2s, 6H, CH₃), 1.462 (d, 3H, J=6.3 Hz, CH₃), 0.974 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 371.1 [M+H]⁺ (MW=370.47);

Elemental analysis: Calculated for C₂₁H₂₂O₄S.3H₂O (%): C, 59.42; H, 6.64. Found (%): C, 59.50; H, 6.32.

Example 29 6,6,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-29, R₁=n-C₃H₇, R₂=R₄═H, R₃═R₅═R₆═CH₃)

(1) 5-hydroxy-4-n-propyl-7-p-methylphenylsulfonyl-coumarin (12, R=n-C₃H₇, R₂═H)

2.64 g (5 mmol) 4-n-propyl-5,7-di(p-methylsulfonyl)-coumarin (8) was dissolved in ml THF and 1.58 g (5 mmol) TBAF was added in order to deprotect the 5-hydroxy protective group. The reaction mixture was stirred for 10 hours at room temperature and then was concentrated in vacuo. The residure was purified by silica gel column chromatography to afford 1.65 g of the title compound in 88% yield as white powder, m.p. 155-157° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 11.261 (s, 1H, OH), 7.790 (m, 2H, Ar—H), 7.499 (m, 2H, Ar—H), 6.521 (d, 1H, J=2.4 Hz, 8-H), 6.472 (d, 1H, J=2.4 Hz, 6-H), 6.104 (s, 1H, 3-H), 2.859 (t, 2H, J=7.5 Hz, CH₂), 2.422 (s, 3H, CH₃), 1.547 (sex, 2H, J=7.5 Hz, 7.2 Hz, CH₂), 0.921 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 375.1 [M+H]⁺ (MW=374.42);

(2) 2,2-dimethyl-8-oxo-10-n-propyl-2H,8H-benzo[2,3-f]dipyranyl-5-p-methylphenylsulfate (13, R₁=n-C₃H₇, R₂═H, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 374 mg (1 mmol) 5-hydroxy-4-n-propyl-7-p-methylphenylsulfonyl-coumarin (12) and 633 mg (4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 385 mg of the title compound in 87% yield as white powder, m.p. 141-143° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 7.778 (m, 2H, Ar—H), 7.465 (m, 2H, Ar—H), 6.643 (s, 1H, 10-H), 6.179 (s, 1H, 3-H), 6.170 (d, 1H, J=9.9 Hz, 8-1H), 5.645 (d, 1H, J=9.9 Hz, 7-H), 2.810 (t, 2H, J=7.5 Hz, CH₂), 2.399 (s, 3H, CH₃), 1.534 (sex, 2H, J=7.5 Hz, 7.2 Hz, CH₂), 1.319 (s, 6H, CH₃), 0.952 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 441.1 [M+H]⁺ (MW=440.52);

Elemental analysis: Calculated for C₂₄H₂₄O₆S (%): C, 65.44; H, 5.49. Found (%): C, 65.43; H, 5.42.

(3) 5-hydroxy-2,2-dimethyl-10-n-propyl-2H-benzo[2,3-f]dipyranyl-8-one (14, R₁=n-C₃H₇, R₂═H, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 10 in example 28, except for using 220 mg (0.5 mmol) 2,2-dimethyl-8-oxo-10-n-propyl-2H,8H-benzo[2,3-f]dipyranyl-5-p-methylphenylsulfate (13) and 236 mg (0.75 mmol) TBAF as starting material to obtain 95 mg of the title compound in 66% yield as yellow powder, m.p. 128-131° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 10.771 (s, 1H, OH), 6.554 (d, 1H, J=9.9 Hz, 8-H), 6.338 (s, 1H, 10-H), 5.907 (s, 1H, 3-H), 5.652 (d, 1H, J=9.9 Hz, 7-H), 2.826 (t, 2H, J=7.5 Hz, CH₂), 1.579 (sex, 2H, J=7.5 Hz, 7.2 Hz, CH₂), 1.433 (s, 6H, CH₃), 0.976 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 287.2 [M+H]⁺ (MW=286.33);

Elemental analysis: Calculated for C₁₇H₁₈O₄.1/4H₂O (%): C, 70.21; H, 6.41. Found (%): C, 70.31; H, 6.39.

(4) 6,6,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-29, R₁=n-C₃H₇, R₂=R₄═H, R₃═R₅═R₆═CH₃)

14.3 mg 5-hydroxy-2,2-dimethyl-10-n-propyl-2H-benzo[2,3-f]dipyranyl-8-one was dissolved in ml BF₃.Et₂O solution. 10 mg (0.1 mmol) crotonyl chloride was added dropwhise. The resulting reaction solution was allowed to 60° C. for two hours, then cooled to room temperature whereupon it was poured into cracked ice-water and extracted with ethyl acetate (3×20). The organic layer was concentrated and the residure was purified by silica gel column chromatography to afford 18 mg of the title compound in 51% yield as white powder, m.p. 112-115° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.566 (d, 1H, J=9.9 Hz, 8-H), 6.086 (s, 1H, 3-H), 5.774 (d, 1H, J=9.9 Hz, 7-H), 4.707 (m, 1H, J=6.3 Hz, 12.0 Hz, 3.9 Hz, 10-H), 2.837 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.708 (dd, 1H, J=12.0 Hz, 16.5 Hz, 11-He), 2.606 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.537 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH₂CH₃), 1.488, 1.450 (2s, 6H, CH₃), 1.439 (d, 3H, J=6.3 Hz, 10-CH₃), 0.963 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 355.1 [M+H]⁺ (MW=354.41);

Example 30 6,6,11-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-30, R₁=n-C₃H₇, R₂═R₃═H, R₄═R₅═R₆═CH₃)

14.3 mg 5-hydroxy-2,2-dimethyl-10-n-propyl-2H-benzo[2,3-f]dipyranyl-8-one (14) was dissolved in 10 ml BF₃.Et₂O solution. 10 ml (01.1 mol) 2-methyl acryloyl chloride was added dropwhise. The resulting reaction solution was allowed to 60° C. for two hours, then cooled to room temperature whereupon it was poured into cracked ice-water and extracted with ethyl acetate (3×20). The organic layer was concentrated and the residure was purified by silica gel column chromatography to afford 19 mg of the title compound in 54% yield as white powder, m.p. 133-134° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.565 (d, 1H, J=9.9 Hz, 8-H), 6.105 (s, 1H, 3-H), 5.789 (d, 1H, J=9.9 Hz, 7-H), 4.630 (dd, 1H, J=5.1 Hz, 11.1 Hz, 10-He), 4.256 (t, 1H, J=11.1 Hz, 10-Ha), 2.846 (m, 3H, 11-CH, 4-CH ₂CH₂CH₃), 1.562 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.492, 1.469 (2s, 6H, CH₃), 1.052 (d, 3H, J=6.9 Hz, 11-CH₃), 0.968 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 355.1 [M+H]⁺ (MW=354.41);

HRESIMS: Calculated for C₂₁H₂₃O₅ ⁺ (m/z): 355.15455. found (m/z): 355.15497.

Example 31 6,6,10-trimethyl-3-fluoro-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-31, R₁=n-C₃H₇, R₂═F, R₃═R₅═R₆═CH₃, R₄═H)

(1) 3-fluoro-4-n-propyl-5,7-dihydroxy-coumarin (6-31, R₁=n-C₃H₇, R₂═F)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 8.1 g (0.046 mol) ethyl 2-fluoro butyrylacetate as starting material to obtain 10.6 g of the title compound in 97% yield as a yellow powder crystalline. m.p. 228-229° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.632 (s, 1H, OH), 10.270 (s, 1H, OH), 6.313 (d, 1H, J=2.4 Hz, 8-H), 6.213 (d, 1H, J=2.4 Hz, 6-H), 2.935 (dt, 2H, J=3.3 Hz, 8.1 Hz, 4-CH ₂CH₂CH₃), 1.596 (sex, 2H, J=8.1 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 0.936 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 239.1 [M+H]⁺ (MW=238.22);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-fluoro-4-n-propyl-2,10-dione (5a-31, R₁=n-C₃H₇, R₂═F, R₃═CH₃, R₄═H) and benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-fluoro-4-n-propyl-2,6-dione (5b-31, R₁=n-C₃H₇, R₂═F, R₃═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.38 g (10 mmol) 3-fluoro-4-n-propyl-5,7-dihydroxy-coumarin (6-31) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 2.1 g of the title compound 5a-31 in 68% yield as a yellowish powder (m.p. 169-171° C.) and 0.34 g of the title compound 5b-31 in 11% yield as a yellowish powder (m.p. 188-189° C.).

Compound 5a-31: ¹HNMR (300 MHz, DMSO-d₆, ppm): 11.882 (s, 1H, OH), 6.351 (s, 1H, 6-H), 4.638 (dt, 1H, J=6.6 Hz, 4.5 Hz, 10.8 Hz, 8-H), 2.960 (dt, 2H, J=3.0 Hz, 7.5 Hz, 4-CH ₂CH₂CH₃), 2.660 (dd, 1H, J=10.8 Hz, 16.2 Hz, 9-He), 2.580 (dd, 1H, J=4.5 Hz, 16.5 Hz, 9-Ha), 1.583 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.389 (d, 3H, J=6.6 Hz, 8-CH₃), 0.938 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 307.1 [M+H]⁺ (MW=306.29);

Elemental analysis: Calculated for C₁₆H₁₅FO₅ (%): C, 62.74; H, 4.94. Found (%): C, 62.89; H, 5.02.

Compound 5b-31: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 13.814 (s, 1H, OH), 6.530 (s, 1H, 10-H), 4.750 (dq, 1H, J=3.0 Hz, 12.3 Hz, 6.3 Hz, 8-H), 2.990 (dd, 1H, J=12.3 Hz, 17.4 Hz, 7-He), 2.931 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.802 (dd, 1H, J=3.0 Hz, 17.4 Hz, 7-Ha), 1.612 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.436 (d, 3H, J=6.3 Hz, 8-CH₃), 0.959 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 307.1 [M+H]⁺ (MW=306.29);

(3) 6,6,10-trimethyl-3-fluoro-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-31, R₁=n-C₃H₇, R₂═F, R₃═R₅═R₆═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 31 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-fluoro-4-n-propyl-2,0-dione (5a-31) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 32 mg of the title compound in 86% yield as off-white powder, m.p. 114-116° C.

¹H-NMR (300 MHz, DMSO-d₆): 6.587 (d, 1H, J=9.9 Hz, 8-H), 5.819 (d, 1H, J=9.9 Hz, 7-H), 4.711 (m, 1H, 10-H), 2.917 (dt, 2H, J=3.6 Hz, 7.5 Hz, 4-CH ₂CH₂CH₃), 2.724 (dd, 1H, J=11.4 Hz, 16.5 Hz, 11-He), 2.629 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.587 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.501, 1.464 (2s, 6H, CH₃), 1.446 (d, 3H, J=6.3 Hz, 10-CH₃), 0.990 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 373.2 [M+H]⁺ (MW=372.40);

Elemental analysis: Calculated for C₂₁H₂₁FO₅ (%): C, 67.73; H, 5.68. Found (%): C, 67.53; H, 5.89.

Example 32 10-methyl-3-fluoro-4,6-di(-n-propyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-32, R₁═R₅=n-C₃H₇, R₂═F, R₃═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 31 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-fluoro-4-n-propyl-2,10-dione (5a-31) and 69 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-hexene as starting material to obtain 24 mg of the title compound in 62% yield as off-white powder, m.p. 123-124° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.665 (dt, 1H, J=9.9 Hz, 3.0 Hz, 8-H), 5.866 (dt, 1H, J=9.9 Hz, 3.6 Hz, 7-H), 5.181 (m, 1H, 6-H), 4.712 (m, 1H, 10-H), 2.926 (m, 2H, CH₂), 2.729 (dd, 1H, J=11.1 Hz, 16.5 Hz, 11-He), 2.639 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.761 (m, 2H, CH₂), 1.562 (m, 2H, CH₂), 1.441 (d, 3H, J=6.3 Hz, 10-CH₃), 1.410 (m, 2H, CH₂), 0.955 (t, 3H, J=7.2 Hz, CH₃), 0.917 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 387.0 [M+H]⁺ (MW=386.42);

Elemental analysis: Calculated for C₂₂H₂₃FO₅.1/2H₂O (%): C, 66.82; H, 6.11. Found (%): C, 66.58; H, 5.94.

Example 33 10-methyl-3-fluoro-4-n-propyl-6-n-butyl-2H, 6H, 12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-33, R₁=n-C₃H₇, R₂═F, R₃═CH₃, R₄═R₆═H, R₅=n-C₄H₉)

Using the same procedure as described in the preparative method of compound 4-1, except for using 31 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-fluoro-4-n-propyl-2,10-dione (5a-31) and 74 mg (0.4 mmol) 1,1-diethoxyl-2-heptene as starting material to obtain 23 mg of the title compound in 58% yield as off-white powder, m.p. 119-121° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.679 (d, 1H, J=10.2 Hz, 8-H), 5.841 (m, 1H, 7-H), 5.128 (m, 1H, 6-H), 4.694 (m, 1H, 10-H), 2.926 (m, 2H, CH₂), 2.705 (m, 2H, CH₂), 2.664 (m, 2H, 11-CH₂), 1.788 (m, 2H, CH₂), 1.559 (m, 2H, CH₂), 1.438 (d, 3H, J=5.4 Hz, 10-CH₃), 1.213 (m, 2H, CH₂), 0.923 (t, 3H, J=7.5 Hz, CH₃), 0.886 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 401.1 [M+H]⁺ (MW=400.45);

Elemental analysis: Calculated for C₂₃H₂₅FO₅.1/3H₂O (%): C, 67.96; H, 6.80. Found (%): C, 67.91; H, 7.02.

Example 34 10-methyl-4,6-di(-n-propyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-34, R₁═R₅=n-C₃H₇, R₃═CH₃, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-2,10-dione (5a-11) and 69 mg (0.4 mmol) 1,1-diethoxyl-2-hexene as starting material to obtain 20 mg of the title compound in 55% yield as off-white powder, m.p. 158-160° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.659 (dt, 1H, J=10.2 Hz, 2.4 Hz, 8-H, 6.112 (s, 1H, 3-H), 5.835 (dt, 1H, J=10.2 Hz, 3.3 Hz, 7-H), 5.120 (m, 1H, 6-H), 4.727 (m, 1H, 10-H), 2.859 (dt, 2H, J=7.5 Hz, 3.9 Hz, 4-CH ₂CH₂CH₃), 2.723 (m, 2H, 6-CH ₂CH₂CH₃), 2.676 (dd, 1H, J=12.0 Hz, 16.5 Hz, 11-He), 2.623 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.788 (m, 2H, 4-CH₂CH ₂C₃), 1.537 (m, 2H, 6-CH₂CH₂CH ₃), 1.440 (d, 3H, J=6.3 Hz, 10-CH₃), 0.961 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃), 0.903 (t, 3H, J=6.9 Hz, 6-CH₂CH₂CH ₃);

ESI-MS (m/z): 369.1 [M+H]⁺ (MW=368.43);

Elemental analysis: Calculated for C₂₂H₂₄O₅.1/3H₂O (%): C, 70.57; H, 6.64. Found (%): C, 70.51; H, 6.92.

Example 35 10-methyl-4-n-propyl-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-35, R₁=n-C₃H₇, R₃═CH₃, R₂═R₄═R₆═H, R₅=n-C₄H₁₉)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-2,10-dione (5a-11) and 74 mg (0.4 mmol) 1,1-diethoxyl-2-heptene as starting material to obtain 21 mg of the title compound in 56% yield as off-white powder, m.p. 138-139° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.630 (dt, 1H, J=10.2 Hz, 5.4 Hz, 8-H), 6.083 (s, 1H, 3-H), 5.807 (dt, 1H, J=10.2 Hz, 3.3 Hz, 7-H), 5.095 (m, 1H, 6-H), 4.676 (m, 1H, 10-H), 2.895 (m, 2H, CH₂), 2.797 (m, 2H, CH₂), 2.627 (m, 2H, 11-CH₂), 1.769 (m, 2H, CH₂), 1.547 (m, 2H, CH₂), 1.435 (d, 3H, J=6.3 Hz, 10-CH₃), 1.299 (m, 2H, CH₂), 0.945 (t, 3H, J=7.5 Hz, CH₃), 0.882 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 383.1 [M+H]⁺ (MW=382.46);

Elemental analysis: Calculated for C₂₃H₂₆O₅.2H₂O (%): C, 66.01; H, 7.47. Found (%): C, 65.97; H, 7.69.

Example 36 6,6,10-trimethyl-4-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-36, R₁=n-C₄H₉, R₂═R₄═H, R₃═R₅═R₆═CH₃)

(1) 4-n-butyl-5,7-dihydroxy-coumarin (6-36, R₁=n-C₄H₉, R₂═H)

Using the same procedure as described in the preparative method of compound (6-1), except for using 7.5 g (0.046 mol) phloroglucinol and 7.92 g (0.046 mol) ethyl pentanoyl acetate as starting material to obtain 9.37 g of the title compound in 87% yield as a yellowish powder crystalline. m.p. 236-237° C.,

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.569 (s, 1H, OH), 10.271 (s, 1H, OH), 6.251 (d, 1H, J=2.4 Hz, 8-H), 6.163 (d, 1H, J=2.4 Hz, 6-H), 5.811 (s, 1H, 3-H), 2.854 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₂CH₃), 1.528 (m, 2H, 4-CH₂CH ₂CH₂CH₃), 1.350 (sex, 2H, J=7.2 Hz, 7.5 Hz, 4-CH₂CH₂CH ₂CH₃), 0.891 (t, 3H, J=7.2 Hz, 4-CH₂CH₂C₂CH₃);

ESI-MS (m/z): 235.1 [M+H]⁺ (MW=234.25);

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-butyl-2,10-dione (5a-36, R₁=n-C₄H₉, R₂═R₄═H, R₃═CH₃) and benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-butyl-8-methyl-2,6-dione (5b-36, R₁=n-C₄H₉, R₂═R₄═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.34 g (10 mmol) 4-n-butyl-5,7-dihydroxy-coumarin (6-36) and 0.92 g (10.7 mmol) crotonic acid as starting material to obtain 1.96 g of the title compound 5a-36 in 65% yield as a white powder (m.p. 145-147° C.) and 0.45 g of the title compound 5b-36 in 15% yield as a white powder (m.p. 178-179° C.).

Compound 5a-36: ¹H NMR (300 MHz, DMSO-d₆, ppm): 11.765 (s, 1H, OH), 6.281 (s, 1H, 6-H), 6.024 (s, 1H, 3-H), 4.634 (m, 1H, 8-H), 2.878 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₂CH₃), 2.646 (dd, 1H, J=11.4 Hz, 16.5 Hz, 9-He), 2.561 (dd, 1H, J=3.9 Hz, 16.5 Hz, 9-Ha), 1.507 (m, 2H, 4-CH₂CH ₂CH₂CH₃), 1.385 (d, 3H, J=6.3 Hz, 8-CH₃), 1.335 (m, 2H, 4-CH₂CH₂CH ₂CH₃), 0.890 (t, 31-1, J=7.2 Hz, 4-CH₂CH₂CH₂CH ₃);

ESI-MS (m/z): 303.2 [M+H]⁺ (MW=302.33);

Elemental analysis: Calculated for C₁₇H₁₈O₅ (%): C, 67.54; H, 6.00. Found (%): C, 67.64; H, 6.07.

Compound 5b-36: ¹H NMR (300 MHz, DMSO-d₆, ppm): 13.913 (s, 1H, OH), 6.466 (s, 1H, 10-H), 6.054 (s, 1H, 3-H), 4.755 (dq, 1H, J=6.3 Hz, 3.0 Hz, 12.3 Hz, 8-H), 2.981 (dd, 1H, J=12.3 Hz, 17.4 Hz, 7-He), 2.887 (t, 21H, J=7.5 Hz, 4-CH ₂CH₂CH₂CH₃), 2.795 (dd, 1H, J=3.0 Hz, 17.4 Hz, 7-Ha), 1.546 (m, 2H, 4-CH₂CH ₂CH₂CH₃), 1.438 (d, 3H, J=6.3 Hz, 8-CH₃), 1.361 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH₂CH ₂CH₃), 0.901 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH₂CH ₃);

ESI-MS (m/z): 303.2 [M+H]⁺ (MW=302.33);

(3) 6,6,10-trimethyl-4-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-36, R₁=n-C₄H₉, R₂═R₄═H, R₃═R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 30 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-butyl-2,10-dione (5a-36) and 63 mg (0.4 mmol) 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 33 mg of the title compound in 89% yield as off-white powder, m.p. 121-122° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.574 (d, 1H, J=10.2 Hz, 8-H), 6.088 (s, 1H, 3-H), 5.779 (d, 1H, J=10.2 Hz, 7-H), 4.709 (m, 1H, 10-H), 2.864 (t, 2H, J=7.5 Hz, CH₂), 2.712 (dd, 1H, J=11.4 Hz, 16.5 Hz, 11-He), 2.611 (dd, 1H, J=3.9 Hz, 16.5 Hz, 11-Ha), 1.541 (m, 2H, CH₂), 1.489, 1.452 (2s, 6H, CH₃), 1.376 (m, 2H, CH₂), 1.441 (d, 3H, J=6.6 Hz, 10-CH₃), 0.903 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 369.1 [M+H]⁺ (MW=368.43);

Elemental analysis: Calculated for C₂₂H₂₄O₅ (%): C, 71.72; H, 6.57. Found (%): C, 71.59; H, 6.70.

Example 37 10-methyl-6-n-propyl-4-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-37, R₁=n-C₄H₉, R₂═R₄═R₆═H, R₃=Cl₃, R₅=n-C₃H₇)

Using the same procedure as described in the preparative method of compound 4-1, except for using 30 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-butyl-2,10-dione (5a-36) and 69 mg (0.4 mmol) 1,1-diethoxyl-2-hexene as starting material to obtain 29 mg of the title compound in 76% yield as off-white powder, m.p. 135-138° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.635 (d, 1H, J=9.9 Hz, 8-H), 6.083 (s, 1H, 3-H), 5.817 (dt, 1H, J=9.9 Hz, 3.0 Hz, 7-H), 5.108 (m, 2H, CH₂), 4.702 (m, 1H, 10-H), 2.855 (m, 2H, CH₂), 2.645 (m, 2H, 11-CH₂), 1.762 (m, 2H, CH₂), 1.436 (d, 3H, J=6.3 Hz, 10-CH₃), 1.358 (m, 2H, CH₂), 1.087 (m, 2H, CH₂), 0.922 (t, 3H, J=7.2 Hz, CH₃), 0.873 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 383.1 [M+H]⁺ (MW=382.46);

Elemental analysis: Calculated for C₂₃H₂₆O₅ (%): C, 72.23; H, 6.85. Found (%): C, 72.16; H, 7.15.

Example 38 10-methyl-4,6-di(n-butyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione

(4-38, R₁═R₅=n-C₄H₉, R₂═R₄═R₆═H, R₃═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 30 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-butyl-2,10-dione (5a-36) and 74 mg (0.4 mmol) 1,1-diethoxyl-2-heptene as starting material to obtain 31 mg of the title compound in 79% yield as off-white powder, m.p. 146-148° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.643 (dd, 1H, J=2.1 Hz, 9.9 Hz, 8-H), 6.089 (s, 1H, 3-H), 5.820 (dt, 1H, J=3.0 Hz, 9.9 Hz, 7-H), 5.108 (m, 2H, CH₂), 4.706 (m, 2H, CH₂), 2.879 (m, 4H, CH₂), 2.665 (m, 2H, 11-CH₂), 1.768 (m, 2H, CH₂), 1.496 (m, 2H, CH₂), 1.436 (m, 2H, CH₂), 0.921 (t, 3H, J=7.2 Hz, CH₃), 0.874 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 397.1 [M+H]⁺ (MW=396.49);

Elemental analysis: Calculated for C₂₄H₂₈O₅ (%): 72.70; H, 7.12. Found (%): C, 72.47; H, 7.14.

Example 39 10-methyl-4-ethyl-6-n-propyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyran yl-2,12-dione (4-39, R₁═C₂H₅, R₂═F, R₃═CH₃, R₅=n-C₃H₇, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-3-fluoro-2,10-dione (5a-10) and 69 mg (0.4 mmol) 1,1-diethoxyl-2-hexene as starting material to obtain 25 mg of the title compound in 68% yield as off-white powder, m.p. 151-153° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.641 (dd, 1H, J=1.8 Hz, 10.2 Hz, 8-H), 5.842 (dt, 1H, J=3.3 Hz, 10.2 Hz, 7-H), 5.148 (m, 1H, 6-H), 4.700 (m, 1H, 10-H), 2.955 (m, 2H, 4-CH ₂CH₃), 2.694 (m, 2H, 11-CH₂), 1.783 (m, 2H, CH₂), 1.440 (d, 3H, J=6.3 Hz, 10-CH₃), 1.768 (m, 2H, CH₂), 0.937 (t, 3H, J=7.2 Hz, CH₃), 0.891 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 373.1 [M+H]⁺ (MW=372.40);

Elemental analysis: Calculated for C₂₁H₂₁FO₅ (%): C, 67.73; H, 5.68. Found (%): C, 67.76; H, 5.61.

Example 40 10-methyl-4-ethyl-3-fluoro-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-40, R₁═C₂H₅, R₂═F, R₃═CH₃, R₅=n-C₄H₉, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-3-fluoro-2,10-dione (5a-10) and 74 mg (0.4 mmol) 1,1-diethoxyl-2-heptene as starting material to obtain 22 mg of the title compound in 56% yield as off-white powder, m.p. 142-143° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.660 (dt, 1H, J=1.8 Hz, 10.2 Hz, 8-H), 5.849 (dt, 1H, J=3.3 Hz, 10.2 Hz, 7-H), 5.155 (m, 1H, 6-H), 4.707 (m, 1H, 10-H), 2.965 (m, 2H, CH₂), 1.791 (m, 2H, CH₂), 1.442 (d, 3H, J=6.0 Hz, 10-CH₃), 1.331 (m, 2H, CH₂), 1.144 (m, 2H, CH₂), 0.894 (t, 3H, J=7.2 Hz, CH₃), 0.872 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 373.1 [M+H]⁺ (MW=372.40);

Elemental analysis: Calculated for C₂₂H₂₃FO₅.1/3H₂O (%): C, 67.34; H, 6.08. Found (%): C, 67.41; H, 6.09.

Example 41 10-methyl-4-n-propyl-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-41, R₁=n-C₃H₇, R₃═CH₃, R₅═C₆H₅, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 31 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-2,10-dione (5a-11) and 82 mg (0.4 mmol) 1,1-diethoxyl-3-phenyl-2-propene as starting material to obtain 27 mg of the title compound in 66% yield as off-white powder, m.p. 96-99° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.451 (m, 5H, 6-Ph), 6.862 (dd, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.257 (dd, 1H, J=1.8 Hz, 3.9 Hz, 6-1H), 6.052 (s, 1H, 3-H), 5.952 (dd, 1H, J=3.9 Hz, 9.9 Hz, 7-H), 4.783 (m, 1H, 10-H), 2.947 (t, 2H, J=7.5 Hz, CH₂), 2.669 (m, 2H, 11-CH₂), 1.647 (sex, 2H, J=7.5 Hz, 7.2 Hz, CH₂), 1.474 (d, 3H, J=6.3 Hz, 10-CH₃), 0.973 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 403.1 [M+H]⁺ (MW=402.45);

Elemental analysis: Calculated for C₂₅H₂₂O₅.H₂O (%): C, 71.41; H, 5.75. Found (%): C, 71.25; H, 5.97.

Example 42 10-methyl-4-ethyl-6-phenyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-42, R₁═C₂H₅, R₂═F, R₃═CH₃, R₅═C₆H₅, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-3-fluoro-2,10-dione (5a-10) and 82 mg (0.4 mmol) 1,1-diethoxyl-3-phenyl-2-propene as starting matrial to obtain 30 mg of the title compound in 75% yield as off-white powder, m.p. 109-111° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.445 (m, 51H, 6-Ph), 6.890 (dd, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.289 (dd, 1H, J=1.8 Hz, 3.9 Hz, 6-H), 6.015 (dd, 1H, J=3.9 Hz, 9.9 Hz, 7-H), 4.756 (m, 1H, 10-H), 3.060 (m, 2H, CH₂), 2.703 (m, 2H, 11-CH₂), 1.481 (d, 3H, J=6.3 Hz, 10-CH₃), 1.040 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 407.1 [M+H]⁺ (MW=406.41);

Elemental analysis: Calculated for C₂₄H₁₉FO₅.1/2H₂O (%): C, 69.39; H, 4.85. Found (%): C, 69.62; H, 4.97.

Example 43 10-methyl-4-n-propyl-6-phenyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-43, R₁=n-C₃H₇, R₂═F, R₃═CH₃, R₅═C₆H₅, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 31 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-n-propyl-3-fluoro-2,10-dione (5a-31) and 82 mg (0.4 mmol) 1,1-diethoxyl-3-phenyl-2-propene as starting material to obtain 28 mg of the title compound in 68% yield as off-white powder, m.p. 128-129° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.457 (m, 5H, 6-Ph), 6.867 (dd, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.267 (dd, 1H, J=1.8 Hz, 3.3 Hz, 6-H), 5.958 (dd, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 4.770 (m, 1H, 10-H), 2.801 (m, 2H, CH₂), 2.688 (m, 2H, 11-CH₂), 1.747 (m, 2H, CH₂), 1.485 (d, 3H, J=6.3 Hz, 10-CH₃), 0.674 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 421.1 [M+H]⁺ (MW=420.44);

Elemental analysis: Calculated for C₂₅H₂₁FO₅.2/3H₂O (%): C, 69.44; H, 5.21. Found (%): C, 69.60; H, 5.41.

Example 44 10-methyl-4-n-butyl-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-44, R₁=n-C₄H₉, R₃═CH₃, R₅═C₆H₅, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 30 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-butyl-2,10-dione (5a-36) and 82 mg (0.4 mmol) 1,1-diethoxyl-3-phenyl-2-propene as starting material to obtain 26 mg of the title compound in 62% yield as off-white powder, m.p. 137-139° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.534 (m, 5H, 6-Ph), 6.857 (dd, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.243 (dd, 1H, J=1.8 Hz, 3.3 Hz, 6-H), 6.043 (s, 1H, 3-H), 5.925 (dd, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 4.746 (m, 1H, 10-H), 2.748 (m, 2H, CH₂), 2.684 (m, 2H, CH₂), 1.470 (dd, 3H, J=1.2 Hz, 6.3 Hz, 10-CH₃), 1.401 (m, 2H, CH₂), 1.224 (m, 2H, CH₂), 0.658 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 417.1 [M+H]⁺ (MW=416.48);

Elemental analysis: Calculated for C₂₆H₂₄O₅.1/3H₂O (%): C, 73.92; H, 5.88. Found (%): C, 73.93; H, 6.02.

Example 45 10-methyl-4-ethyl-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-45, R₁═C₂H₅, R₃═CH₃, R₅═C₆H₅, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 27 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-2,10-dione (5a-9) and 82 mg (0.4 mmol) 1,1-diethoxyl-3-phenyl-2-propene as starting material to obtain 25 mg of the title compound in 64% yield as off-white powder, m.p. 126-128° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.437 (m, 5H, 6-Ph), 6.862 (dd, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.286 (dd, 1H, J=1.8 Hz, 3.3 Hz, 6-H), 6.060 (s, 1H, 3-H), 5.979 (dd, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 4.753 (m, 1H, 10-H), 3.040 (m, 2H, CH₂), 2.690 (m, 2H, CH₂), 1.471 (dd, 3H, J=2.1 Hz, 6.3 Hz, 10-CH₃), 1.221 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 389.1 [M+H]⁺ (MW=388.42);

Elemental analysis: Calculated for C₂₄H₂₀O₅.1/2H₂O (%): C, 72.53; H, 5.33. Found (%): C, 72.60; H, 5.83.

Example 46 10-methyl-4-ethyl-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-46, R₁═C₂H₅, R₃═CH₃, R₅=n-C₄H₉, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 27 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-2,10-dione (5a-9) and 74 mg (0.4 mmol) 1,1-diethoxyl-2-heptene as starting material to obtain 29 mg of the title compound in 78% yield as off-white powder, m.p. 119-121° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.632 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.096 (s, 1H, 3-H), 5.809 (dt, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 5.467 (m, 1H, 6-H), 4.688 (m, 1H, 10-H), 2.915 (m, 2H, CH₂), 2.654 (m, 2H, 11-CH₂), 1.790 (m, 2H, CH₂), 1.435 (dd, 3H, J=3.6 Hz, 6.0 Hz, 10-CH₃), 1.340 (m, 4H, CH₂), 1.168 (t, 3H, J=7.2 Hz, CH₃), 0.881 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 369.1 [M+H]⁺ (MW=368.43);

Elemental analysis: Calculated for C₂₂H₂₄O₅.1/2H₂O (%): C, 70.01; H, 6.68. Found (%): C, 69.98; H, 6.89.

Example 47 10-methyl-4-ethyl-6-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-47, R₁═C₂H₅, R₃═CH₃, R₅=n-C₃H₇, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 27 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-2,10-dione (5a-9) and 69 mg (0.4 mmol) 1,1-diethoxyl-2-hexene as starting material to obtain 29 mg of the title compound in 78% yield as off-white powder, m.p. 119-121° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.637 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.098 (s, 1H, 3-H), 5.819 (dt, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 5.477 (m, 1H, 6-H), 4.701 (m, 1H, 10-H), 2.949 (m, 2H, CH₂), 2.665 (m, 2H, 11-CH₂), 1.764 (m, 2H, CH₂), 1.438 (dd, 3H, J=3.0 Hz, 6.3 Hz, 10-CH₃), 1.170 (t, 3H, J=7.2 Hz, CH₃), 1.116 (m, 4H, CH₂), 0.899 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 355.1 [M+H]⁺ (MW=354.41);

Elemental analysis: Calculated for C₂₁H₂₂O₅.1/2H₂O (%): C, 69.41; H, 6.38. Found (%): C, 69.62; H, 6.75.

Example 48 10-methyl-4,6-di(-n-propyl)-3,-chloro-2H,6H,2H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyrany 1-2,12-dione (4-48, R₁═R₅=n-C₃H₇, R₂═Cl, R₃═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 32 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-3-chloro-2,10-dione (5a-20) and 69 mg (0.4 mmol) 1,1-diethoxyl-2-hexene as starting material to obtain 29 mg of the title compound in 73% yield as off-white powder, m.p. 140-142° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.671 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 5.878 (dt, 1H, J=2.7 Hz, 9.9 Hz, 7-H), 5.177 (m, 1H, 6-H), 4.734 (m, 1H, 10-H), 3.118 (t, 2H, J=7.2 Hz, CH₂), 2.662 (m, 2H, 11-CH₂), 1.785 (m, 2H, CH₂), 1.551 (m, 2H, CH₂), 1.447 (d, 3H, J=6.3 Hz, 10-CH₃), 1.002 (t, 3H, J=7.2 Hz, CH₃), 0.939 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 403.1 M⁺ (MW=402.88);

Elemental analysis: Calculated for C₂₂H₂₃ClO₅ (%): C, 65.59; H, 5.75. Found (%): C, 65.36; H, 5.74.

Example 49 10-methyl-4-n-propyl-3-chloro-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-49, R₁=n-C₃H₇, R₂═Cl, R₃═CH₃, R₅=n-C₄H₉, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 32 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-3-chloro-2,10-dione (5a-20) and 74 mg (0.4 mmol) 1,1-diethoxyl-2-heptene as starting material to obtain 30 mg of the title compound in 71% yield as off-white powder, m.p. 146-149° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.664 (dt, 1H, J=1.8 Hz, 10.2 Hz, 8-H), 5.871 (dt, 1H, J=3.3 Hz, 10.2 Hz, 7-H), 5.175 (m, 1H, 6-H), 4.730 (m, 1H, 10-H), 3.110 (t, 2H, J=7.8 Hz, CH₂), 2.673 (m, 2H, 11-CH₂), 1.803 (m, 2H, CH₂), 1.550 (m, 2H, CH₂), 1.446 (d, 3H, J=6.3 Hz, 10-CH₃), 1.343 (m, 4H, CH₂), 1.003 (t, 3H, J=7.2 Hz, CH₃), 0.890 (t, 3H, J=6.6 Hz, CH₃);

ESI-MS (m/z): 417.1 M⁺ (MW=416.91);

Elemental analysis: Calculated for C₂₃H₂₅ClO₅.1/8H₂O (%): C, 65.91; H, 6.07. Found (%): C, 65.90; H, 6.23.

Example 50 1-methyl-4-n-propyl-3-chloro-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-12-dione (4-50, R₁=n-C₃H₇, R₂═Cl, R₃═CH₃, R₅═C₆H₅, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 32 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-3-chloro-2,10-dione (5a-20) and 82 mg (0.4 mmol) 1,1-diethoxyl-3-phenyl-2-propene as starting material to obtain 30 mg of the title compound in 71% yield as off-white powder, m.p. 152-154° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.449 (m, 5H, 6-Ph), 6.852 (dq, 1H, J=1.8 Hz, 10.2 Hz, 8-H), 6.275 (dq, 1H, J=3.0 Hz, 1.8 Hz, 6-H), 5.952 (dq, 1H, J=3.0 Hz, 10.2 Hz, 7-H), 4.771 (m, 1H, 10-H), 2.967 (m, 2H, CH₂), 2.715 (m, 2H, 11-CH₂), 1.480 (dd, 3H, J=0.9 Hz, 6.3 Hz, 10-CH₃), 1.318 (m, 2H, CH₂), 0.675 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 437.1 M⁺ (MW=436.90);

Elemental analysis: Calculated for C₂₅H₂₁ClO₅ (%): C, 68.73; H, 4.84. Found (%): C, 68.53; H, 5.14.

Example 51 11-methyl-4,6-di(-n-propyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-51, R₁═R₅=n-C₃H₇, R₂═R₃═R₆═H, R₄═CH₃)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-9-methyl-4-n-propyl-2,10-dione (5a-51, R₁=n-C₃H₇,R₂═R₃═H, R₄═CH₃)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 2.20 g (10 mmol) 4-n-propyl-5,7-dihydroxy-coumarin (6-11) and 0.92 g (10.7 mmol) 2-methylpropenoic acid as starting material to obtain 1.93 g of the title compound 5a-11 in 67% yield as a off-white powder, m.p. 164-166° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.961 (s, 1H, OH), 6.450 (s, 1H, 6-H), 6.052 (s, 1H, 3-H), 3.154 (dd, 1H, J=6.6 Hz, 15.6 Hz, 10-He), 2.907 (m, 3H, 4-CH₂, 11-CH), 2.642 (dd, 1H, J=12.3 Hz, 15.6 Hz, 10-Ha), 1.588 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.250 (d, 3H, J=6.6 Hz, 11-CH₃), 0.939 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 289.1 [M+H]⁺ (MW=288.30);

Elemental analysis: Calculated for C₁₆H₁₆O₅ (%): C, 66.66; H, 5.59. Found (%): C, 66.55; H, 6.10.

(2) 11-methyl-4,6-di(-n-propyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-51, R₁═R₅=n-C₃H₇, R₂═R₃═R₆═H, R₄═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using 28 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-9-methyl-4-n-propyl-2,10-dione (5a-51) and 69 mg (0.4 mmol) 1,1-diethoxyl-2-hexene as starting material to obtain 25 mg of the title compound in 69% yield as off-white powder, m.p. 148-150° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.633 (d, 1H, J=10.2 Hz, 8-H), 6.101 (s, 1H, 3-H), 5.840 (d, 1H, J=10.2 Hz, 7-H), 5.124 (m, 1H, 6-H), 4.613 (m, 1H, 10-He), 4.258 (m, 1H, 10-Ha), 2.857 (m, 3H, 11-CH, 4-CH ₂CH₂CH₃), 1.765 (m, 2H, 6-CH ₂CH₂CH₃), 1.535 (m, 4H, CH₂), 1.059 (d, 3H, J=6.9 Hz, 11-CH₃), 0.933 (m, 6H, CH₃);

ESI-MS (m/z): 369.1 [M+H]⁺ (MW=368.43);

Elemental analysis: Calculated for C₂₂H₂₄O₅.4/3H₂O (%): C, 67.33; H, 6.85. Found (%): C, 67.42; H, 6.58.

Example 52 10-methyl-4-n-propyl-6-ethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-52, R₁=n-C₃H₇, R₃═CH₃, R₅═C₂H₅, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 28 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-2,10-dione (5a-11) and 63 mg (0.4 mmol) 1,1-diethoxyl-2-pentene as starting material to obtain 24 mg of the title compound in 68% yield as off-white powder, m.p. 139-141° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.669 (dt, 1H, J=2.4 Hz, 9.9 Hz, 8-H), 6.098 (s, 1H, 3-H), 5.821 (dt, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 5.478 (m, 1H, 6-H), 4.695 (m, 1H, 10-H), 2.959 (m, 2H, CH₂), 2.661 (m, 2H, 11-CH₂), 1.823 (m, 2H, CH₂), 1.562 (m, 2H, CH₂), 1.433 (d, 3H, J=6.3 Hz, 10-CH₃), 0.973 (t, 3H, J=7.2 Hz, CH₃), 0.925 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 355.1 [M+H]⁺ (MW=354.41);

Elemental analysis: Calculated for C₂₁H₂₂O₅.1/2H₂O (%): C, 69.41; H, 6.38. found (%): C, 69.27; H, 6.81.

Example 53 10-methyl-4,6-diethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-53, R₁═R₅═C₂H₅, R₃═CH₃, R₂═R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 27 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-2,10-dione (5a-9) and 63 mg (0.4 mmol) 1,1-diethoxyl-2-pentene as starting material to obtain 22 mg of the title compound in 64% yield as off-white powder, m.p. 129-131° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.664 (d, 1H, J=9.9 Hz, 8-H), 6.107 (s, 1H, 3-H), 5.819 (m, 1H, 7-H), 5.480 (m, 1H, 6-H), 4.780 (m, 1H, 10-H), 2.932 (m, 2H, CH₂), 2.663 (m, 2H, 1-CH₂), 1.771 (m, 2H, CH₂), 1.434 (d, 3H, J=6.3 Hz, 10-CH₃), 1.151 (m, 6H, CH₃);

ESI-MS (m/z): 341.1 [M+H]⁺ (MW=340.38);

Elemental analysis: Calculated for C₂₀H₂₀O₅.5/12H₂O (%): C, 69.05; H, 6.04. Found (%): C, 69.16; H, 6.42.

Example 54 10-methyl-4-n-propyl-6-ethyl-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyran yl-2,12-dione (4-54, R₁=n-C₃H₇, R₂═C₁, R₃═CH₃, R₅═C₂H₅, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 32 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-3-chloro-2,10-dione (5a-20) and 63 mg (0.4 mmol) 1,1-diethoxyl-2-pentene as starting material to obtain 27 mg of the title compound in 71% yield as off-white powder, m.p. 145-147° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.670 (d, 1H, J=10.2 Hz, 8-H), 5.853 (m, 1H, 7-H), 5.128 (m, 1H, 6-H), 4.724 (m, 1H, 10-H), 3.097 (t, 2H, J=7.8 Hz, CH₂), 2.715 (m, 2H, 11-CH₂), 1.818 (m, 2H, CH₂), 1.545 (m, 2H, CH₂), 1.446 (d, 3H, J=6.3 Hz, 10-CH₃), 0.987 (t, 3H, J=7.2 Hz, CH₃), 0.937 (t, 3H, J=7.5 Hz, CH₃);

ESI-MS (m/z): 389.1 M⁺ (MW=388.85);

Elemental analysis: Calculated for C₂₁H₂₁ClO₅.1/4H₂O, calculated (%): C, 64.12; H, 5.51. Found (%): C, 64.11; H, 5.43.

Example 55 10-methyl-4,6-diethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-55, R₁═R₅═C₂H₅, R₂═F, R₃═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 29 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-ethyl-3-fluoro-2,10-dione (5a-10) and 63 mg (0.4 mmol) 1,1-diethoxyl-2-pentene as starting material to obtain 25 mg of the title compound in 70% yield as off-white powder, m.p. 144-146° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.662 (dt, 1H, J=2.4 Hz, 10.2 Hz, 8-H), 5.840 (dt, 1H, J=2.7 Hz, 10.2 Hz, 7-H), 5.114 (m, 1H, 6-H), 4.712 (m, 1H, 10-H), 2.965 (m, 2H, CH₂), 2.669 (m, 2H, 11-CH₂), 1.817 (m, 2H, CH₂), 1.441 (d, 3H, J-6.0 Hz, 10-CH₃), 1.193 (t, 3H, J=7.2 Hz, CH₃), 1.138 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 359.1 [M+H]⁺ (MW=358.37);

Elemental analysis: Calculated for C₂₀H₁₉FO₅. 1/3H₂O (%): C, 65.93; H, 5.44. Found (%): C, 65.88; H, 5.60.

Example 56 10-methyl-4-n-propyl-6-ethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyrany 1-2,12-dione (4-56, R₁=n-C₃H₇, R₂═F, R₃═CH₃, R₅═C₂H₅, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using 31 mg (0.1 mmol) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-propyl-3-fluoro-2,10-dione (5a-31) and 63 mg (0.4 mmol) 1,1-diethoxyl-2-pentene as starting material to obtain 24 mg of the title compound in 65% yield as off-white powder, m.p. 147-149° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.675 (dt, 1H, J=1.8 Hz, 10.2 Hz, 8-H), 5.850 (dt, 1H, J=3.3 Hz, 10.2 Hz, 7-H), 5.122 (m, 1H, 6-H), 4.706 (m, 1H, 10-H), 2.922 (m, 2H, CH₂), 2.658 (m, 2H, 11-CH₂), 1.831 (m, 2H, CH₂), 1.577 (m, 2H, CH₂), 1.441 (d, 3H, J=6.0 Hz, 10-CH₃), 0.989 (t, 3H, J=7.2 Hz, CH₃), 0.926 (t, 3H, J=7.2 Hz, CH₃);

ESI-MS (m/z): 373.1 [M+H]⁺ (MW=372.40);

Elemental: C₂₁H₂₁FO₅, calculated (%): C, 67.73; H, 5.68. Found (%): C, 67.54; H, 5.72.

Example 57 6,6,10-trimethyl-4-n-propyl-10-bromomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tri pyranyl-2,12-dione (4-57, R₁=n-C₃H₇, R₃=BrCH₂, R₅═R₆═CH₃, R₂═R₄═H)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-bromomethyl-4-n-propyl-2,10-dione (5a-57, R₁=n-C₃H₇, R₂═H, R₃=BrCH₂, R₄═H) and benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-bromomethyl-4-n-propyl-2,6-dione (5b-57, R₁=n-C₃H₇, R₂═H, R₃═BrCH₂, R₄═H)

Using the same procedure as described in the preparative method of compound 5a-1, except for using 0.44 g (2 mmol) 4-n-propyl-5,7-dihydroxyl-coumarin (6-11) and 0.445 g (3 mmol) 4-bromo-crotonic acid as starting material to obtain 0.157 g of the title compound 5a-57 in 43% yield as a yellowish powder m.p. 201-203° C., and 0.136 g of the title compound 5b-57 in 37% yield as a white powder m.p. 228-229° C.

Compound 5a-57: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 11.892 (s, 1H, OH), 6.337 (s, 1H, 6-H), 6.062 (s, 1H, 3-H), 4.787 (m, 1H, 8-H), 3.893 (dd, 1H, J=3.3 Hz, 11.4 Hz, BrCH₂), 3.795 (dd, 1H, J=6.3 Hz, 11.4 Hz, BrCH₂), 2.881 (t, 2H, J=6.31 Hz, 4-CH ₂CH₂CH₃), 2.823 (dd, 1H, 12.3 Hz, 16.5 Hz, 9-CH), 2.629 (dd, 1H, J=3.3 Hz, 16.5 Hz, 9-CH), 1.562 (sex, 2H, J=7.2 Hz, 7.5 Hz, 4-CH₂CH ₂CH₃), 0.931 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 366.8/368.8 M⁺ (MW=367.20);

Anal. Calcd. for C₁₆H₁₅BrO₅: C, 52.34; H, 4.12. Found: C, 52.23; H, 4.04.

Compound 5b-57: ¹H-NMR (300 MHz, DMSO-d₆, ppm): 13.806 (s, 1H, 5-OH), 6.527 (s, 1H, 10-H), 6.081 (s, 1H, 3-H), 4.943 (m, 1H, 8-H), 3.949 (dd, 1H, J=3.3 Hz, 11.4 Hz, BrCH₂), 3.851 (dd, 1H, J=5.4 Hz, 11.4 Hz, BrCH₂), 3.1.48 (dd, 1H, J=12.3 Hz, 17.1 Hz, 7-CH), 2.890 (m, 2H, 4-CH ₂CH₂CH₃), 2.856 (dd, 1H, J=3.3 Hz, 17.1 Hz, 7-CH), 1.594 (sex, 2H, J=7.2 Hz, 7.5 Hz, 4-CH₂CH ₂CH₃), 0.953 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 366.8/368.8 M⁺ (MW=367.20);

HRESIMS obsd. m/z: 367.02119, calcd. for C₁₆H₁₆BrO₅ ⁺: 367.01811.

(2) 6,6,10-trimethyl-4-n-propyl-10-bromomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyran yl-2,12-dione (4-57,R₁=n-C₃H₇, R₃=BrCH₂, R₅═R₆═CH₃, R₂═R₄═H)

To a solution of 0.37 g (1 mmol) compound 5a-57 in microwave reaction tube, 2 ml toluene solvent and 1 ml acetal (13) and two drops of pyridine was added. The reaction solution was irradiated with microwave at 150 watt, 140° C. for 20 min. Then purification by silica-gel column chromatography, the title compound 4-57 was obtainede in 87% yield as off-white powder, m. p. 136-138° C.; ¹H-NMR (300 MHz, DMSO-d6, ppm): 6.617 (d, 1H, J=9.9 Hz, 8-H), 6.126 (s, 1H, 3-H), 5.836 (d, 1H, J=9.9 Hz, 7-H), 4.840 (m, 1H, 10-H), 3.940 (dd, 1H, J=3.3 Hz, 11.4 Hz, BrCH2), 3.838 (dd, 1H, J=6.6 Hz, 11.4 Hz, BrCH2), 2.858 (t, 2H, J=7.2 Hz, 4-CH2CH2CH3), 2.825 (m, 1H, 11-CH2), 2.687 (dd, 1H, J=3.0 Hz, 16.2 Hz, 11-CH2), 1.575 (m, 2H, 4-CH2CH2CH3), 1.512, 1.469 (2s, 6H, 6-CH3), 0.969 (t, 3H, J=7.2 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 433.1/435.1 M⁺ (MW=433.30);

HRESIMS obsd. m/z 433.0627, calcd. for C21H22BrO5+433.0650.

Example 58 6,6,10-trimethyl-4-n-propyl-10-azidomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tri pyranyl-2,12-dione (4-58,R₁=n-C₃H₇, R₃=N₃CH₂, R₅═R₆═CH₃, R₂═R₄═H)

(1) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-azidomethyl-4-n-propyl-2,10-dione (5a-58, R₁-n-C₃H₇, R₂═H R₃═N₃CH₂, R₄H)

Compound 5a-57 (0.37 g, 1 mmol) was dissolved in 6 ml DMF, then 0.13 g (2 mmol) NaN₃ was added. The resulting reaction mixture was heated to 70° C. and stirred for 1 hour and then concentrated to give viscose oil which was purified by silica gel column chromatography to afford 0.28 g of the title compound in 85% yield as white powder, m. p. 208-209.5° C.

¹H NMR (300M Hz, DMSO-d₆, ppm): 11.867 (br, 1H, OH), 6.322 (S, 1H, Ph-H), 6.051 (s, 1H, 3-H), 4.768 (m, 1H, 10-H), 3.666 (d, 2H, J=8.4 Hz, NCH2), 2.859 (m, 2H, 4-CH2CH2CH3), 2.792 (d, 1H, J=3 Hz, 11-CH2), 2.596 (d, 1H, J=3 Hz, 11-CH2), 1.560 (m, 2H, 4-CH2CH2CH3), 0.928 (t, 31H, J=7.5 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 330.01 [M+F](MW=329.31).

(2) 6,6,10-trimethyl-4-n-propyl-10-azidomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyran yl-2,12-dione (4-58,R₁=n-C₃H₇, R₃=N₃CH₂, R₅═R₆═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-57, except for using 165 mg (0.5 mmol) Compound 5a-58 and 1 ml acetal as starting material to obtain 150 mg of the title compound in 68% yield as yellowish powder, m.p. 116-117° C.; ¹H NMR (300M Hz, DMSO-d₆, ppm): 6.608 (d, 1H, J=10 Hz, 8-H), 6.133 (s, 1H, 3-H), 5.840 (d, 1H, J=10 Hz, 7-H), 4.629 (m, 1H, 10-H), 3.716 (m, 2H, NCH2), 2.859 (m, 2H, 4-CH2CH2CH3), 2.822 (1H, 11-CH2), 2.628 (d, 1H, J=3 Hz, 11-CH2), 1.580 (m, 2H, 4-CH2CH2CH3), 1.510, 1.471 (2s, 6H, 6-CH3), 0.973 (t, 3H, J=7.5 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 396.14 [M+H]⁺ (MW=395.41).

Example 59 6,6,10-trimethyl-4-n-propyl-10-aminomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-59, R₁=n-C₃H₇, R₃=NH₂CH₂, R₅═R₆═CH₃, R₂═R₄═H)

0.2 g compound 4-58 (0.5 mmol) was dissolved in 20 nil THF and then 0.45 g SnCl₂.2H₂O (2 mmol) and 1 ml concentrated hydrochloric acid were added. The resulting mixture was refluxed with stirring for 3 hours and then 10 ml water was added to quench the reaction, then concentrated ammonia water was added dropwise to adjust the PH of reaction solution to 8-9. The pale white solid was filtrated off and the filtrate was extracted 3 times with ethyl acetate. The combined organic phase was dried and concentrated to give brown oil which was purified by anti-phase C-18 column chromatography to afford 0.11 g of the title compound 4-59 in 59.5% yield as yellowish powder, m. p. >220° C., decomposition°

¹H NMR (500M Hz, DMSO-d₆, ppm): 6.841 (d, 1H, J=10 Hz, 8-H), 6.535 (br, 1H, NH), 6.131 (s, 1H, 3-H), 5.806 (d, 1H, J=10 Hz, 7-H), 4.634 (m, 1H, 10-H), 3.086 (m, 2H, NCH2), 2.854 (m, 2H, 4-CH2CH2CH3), 2.820 (1H, 11-CH2,), 2.618 (d, 1H, J=6 Hz, 11-CH2), 1.561 (m, 2H, 4-CH2CH2CH3), 1.514, 1.478 (2s, 6H, 6-CH3), 0.974 (t, 3H, J=7.5 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 370.26 [M+H^(+]) (MW=369.41).

Example 60 6,6-dimethyl-4-n-propyl-10-(p-fluorophenylureido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-60,R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

18.5 mg compound 4-59 (0.05 mmol) was dissolved in 10 ml THF and then 14 mg (0.1 mmol) 4-fluorophenyl isocyanate was added and refluxed with stirring for 3 hours. Then the reaction mixture was purified by silica gel column chromatography to afford 11.8 mg of the title compound 4-60 in 60.8% yield as white powder, m. p. 119-120.5° C.; ¹H-NMR (300 MHz, DMSO-d₆, ppm): 8.623 (s, 1H, NH), 7.392 (pent, 2H, Ar—H, J=4.8 Hz, J=2.1 Hz), 7.056 (t, 2H, J=9 Hz, Ar—H), 6.696 (d, 1H, J=10.2 Hz, 8-H), 6.468 (t, 1H, J=5.7 Hz, NH), 6.119 (s, 1H, 3-H), 5.794 (d, 1H, J=10.2 Hz, 7-H), 4.643 (m, 1H, 10-H), 3.506 (m, 2H, NCH2), 2.856 (m, 2H, 4-CH2CH2CH3), 2.760 (dd, 1H, J=14.4 Hz, J=3.6 Hz, 11-CH2), 2.580 (dd, 1H, J=14.4 Hz, J=3 Hz, 11-CH2), 1.564 (m, 2H, 4-CH2CH2CH3), 1.504, 1.467 (2s, 6H, 6-CH3), 0.970 (t, 3H, J=7.2 Hz, 4-CH2CH2CH3); ESI-MS (m/z): 507.18 [M+H⁺](MW=506.52);

HRESIMS obsd. m/z 507.1925, calcd. for C₂₈H₂₈N₂O₆F⁺ 507.1920.

Example 61 6,6-dimethyl-4-n-propyl-10-(p-acetylaminophenylsulfonamido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-61, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-60, except for using compound 4-59 (18.5 mg, 0.05 mmol), 0.1 mmol 4-acetylaminophenylsulfonyl chloride and 0.1 mmol pyridine as starting material to obtain the title compound in 61% yield as white powder, m. p. 127-128.5° C.; ¹H NMR (600M Hz, DMSO-d₆, ppm): 10.343 (s, 1H, NH), 8.01 (s, 1H, NH), 7.95 (s, 2H, Ph-H), 7.93 (s, 2H, Ph-H), 6.661 (d, 1H, J=100 Hz, 8-H), 6.105 (s, 1H, 3-H), 5.796 (d, 1H, J=10 Hz, 7-H), 4.541 (m, 1H, 10-H), 3.226 (d, 1H, J=14.4 Hz, NCH), 3.157 (m, 1H, NCH), 2.848 (m, 211, J=6 Hz, 4-CH2CH2CH3), 2.752 (d, 1H, J=3 Hz, 11-CH2), 2.543 (d, 1H, J=3 Hz, 11-CH2), 2.066 (s, 3H, CH3), 1.560 (m, 2H, 4-CH2CH2CH3), 1.500, 1.464 (2s, 6H, 6-CH3), 0.969 (t, 3H, J=7.2 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 567.74 [M+H⁺] (MW=566.62).

Example 62 6,6-dimethyl-4-n-propyl-10-(p-fluorophenylsulfonamido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-62,R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-60, except for using 18.5 mg (0.05 mmol) compound 4-59 and 0.1 mmol 4-fluorophenylsulfonyl chloride as starting material to obtain the title compound in 46.6% yield as white powder, m. p. 129-131° C.; ¹H-NMR (300 MHz, DMSO-d₆, ppm): 8.191 (t, 1H, NH), 7.904 (dd, 2H, J=8.7 Hz, J=5.1 Hz, Ar—H), 7.427 (t, 2H, J=9 Hz, Ar—H), 6.657 (d, 1H, J=10.2 Hz, 8-H), 6.118 (s, 1H, 3-H), 5.792 (d, 1H, J=9.9 Hz, 7-H), 4.576 (m, 1H, 10-H), 3.179 (m, 2H, NCH2), 2.840 (t, 2H, 4-CH2CH2CH3), 2.742 (d, 1H, J=14.5 Hz, 11-CH2), 2.564 (1H, 11-CH2), 1.562 (m, 2H, 4-CH2CH2CH3), 1.503, 1.469 (2s, 6H, 6-CH3), 0.969 (t, 3H, J=7.2 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 528.28[M+H⁺] (MW=527.56);

HRESIMS obsd. m/z 528.1490, calcd. for C₂₇H₂₇NO₇FS⁺ 528.1492.

Example 63 6,6-dimethyl-4-n-propyl-10-(p-methoxylphenyl sulfonamido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-63, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-60, except for using 18.5 mg (0.05 mmol) compound 4-59 and 0.1 mmol 4-methoxylphenylsulfonyl chloride as starting material to obtain the title compound in 54.8% yield as off-white powder, m. p. 108-109° C.; ¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.981 (t, 1H, J=6.3 Hz, NH), 7.747 (dd, 2H, J=9 Hz, Ph-H), 7.082 (dd, 2H, J=9 Hz, Ph-H), 6.672 (d, 1H, J=10 Hz, 8-H), 6.116 (s, 1H, 3-H), 5.774 (d, 1H, J=10 Hz, 7-H), 4.559 (m, 1H, 10-H), 3.814 (s, 3H, OCH₃), 3.142 (m, 2H, NCH2), 2.860 (t, 2H, J=7.2 Hz, 4-CH2CH2CH3), 2.758 (d, 1H, J=3.9 Hz, 11-CH2), 2.562 (d, 1H, J=3.3 Hz, 11-CH2), 1.551 (m, 2H, 4-CH2CH2CH3), 1.505, 1.470 (2s, 6H, 6-CH3), 0.971 (t, 3H, J=7.21 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 540.23 [M+H⁺] (MW=539.6);

HRESIMS obsd m/z 540.1705, calcd for C₂₈H₃₀NO₄S⁺ 540.1692

Example 64 6,6-dimethyl-4-n-propyl-10-(o-methoxyl-phenylthioureido)methylene-2H¹⁶H,12H-benz o[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-64, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-60, except for using 18.5 mg (0.05 mmol) compound 4-59 and 0.1 mmol 2-methoxylphenylisocyanate as starting material to obtain the title compound in 55.8% yield as white powder, m. p. 193-194° C.; ¹H-NMR (300 MHz, DMSO-d₆, ppm): 9.148 (s, 1H, NH), 8.076 (s, 1H, NH), 7.758 (s, 1H, Ar—H), 7.153 (t, 1H, J=8 Hz, Ar—H), 7.045 (d, 1H, J=8.5 Hz, Ar—H), 6.910 (t, 1H, J=7.5 Hz, Ar—H), 6.687 (d, 1H, J=10 Hz, 8-H), 6.124 (s, 1H, 3-H), 5.819 (d, 1H, J=100 Hz, 7-H), 4.799 (m, 1H, 10-H), 3.952 (m, 2H, NCH2), 3.785 (s, 3H, OCH₃), 2.857 (t, 2H, J=6 Hz, 4-CH2CH2CH3), 2.815 (dd, 1H, J=14.4 Hz, J=4 Hz, 11-CH2), 2.659 (dd, 1H, J=14.4 Hz, J=4 Hz, 11-CH2), 1.747 (m, 2H, 4-CH2CH2CH3), 1.514, 1.477 (2s, 6H, 6-CH3), 0.974 (t, 3H, J=7.5 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 535.41 [M+H⁺] (MW=534.62);

HRESIMS obsd. m/z 535.1906, calcd. for C₂₉H₃₁N₂O₆S⁺ 535.18970.

Example 65 6,6-dimethyl-4-n-propyl-10-tetrahydropyrrolylmethylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-65, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

2 equivlent cyclopentylamine was added into the solution of compound 4-57 (0.02 mmol) in THF and the mixture was stirred overnight at room temperature. After concentration and purification by silica gel column chromatography with petroleum ether/ethyl acetate as the eluent, 6.1 mg compound 4-65 was obtained as brown-yellow powder in 72% yield, m. p. 148-149° C. ¹H-NMR (500 MHz, DMSO-d₆, ppm): 6.442 (dd, 1H, J=2.0 Hz, 10.0 Hz, 8-H), 6.172 (s, 1H, 3-H), 5.579 (dd, 1H, J=2.5 Hz, 10.0 Hz, 7-H), 4.776 (m, 1H, 10-H), 3.457 (m, 2H, CH₂), 3.114 (m, 2H, 4-CH ₂CH₂CH₃), 2.355 (m, 4H, CH₂), 2.221 (m, 2H, 11-CH₂), 1.846 (m, 4H, CH₂), 1.723 (m, 2H, 4-CH₂CH ₂CH₃), 1.263, 1.250 (2s, 6H, 6-CH₃), 0.873 (t, 3H, J=7.0 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 424.1 [M+H]⁺ (MW=423.51);

HRESIMS obsd. m/z 424.2125, calcd. for C₂₅H₃₀NO₅ ⁺ 424.212390.

Example 66 6,6-dimethyl-4-n-propyl-10-piperidinylmethylene-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-66,R₁=n-C₃H₇, R₅═R₅═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-65, except for using 4-57 and 2 equivlent cyclohexylamine as starting material to obtain 6 mg of the title compound 4-66 in 69% yield as off-white powder, m. p. 154-155° C.

¹H-NMR (500 MHz, DMSO-d₆, ppm): 6.448 (d, 1H, J=10.0 Hz, 8-H), 6.149 (d, 1H, J=9.5 Hz, 3-H), 5.696 (d, 1H, J=10.0 Hz, 7-H), 4.786 (m, 1H, 10-H), 3.418 (m, 2H, CH₂), 3.067 (m, 2H, 4-CH ₂CH₂CH₃), 2.286 (m, 2H, 11-CH₂), 2.083 (m, 4H, 2CH₂), 1.471 (m, 2H, 4-CH₂CH ₂CH₃), 1.344, 1.310 (2s, 6H, 6-CH₃), 1.296 (m, 6H, 3CH₂), 0.864 (t, 3H, J=7.5 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 438.1 [M+H]⁺ (MW=437.54);

HRESIMS obsd. m/z 438.2282, calcd. for C₂₆H₃₂NO₅ ⁺ 438.228040.

Example 67 5-hydroxy-6-(1′-isopropyl-1′H-pyrrolyl-2′-ene)-2,2-dimethyl-10-n-propyl-2H-benzo[2,3-f]-pyranyl-8-one (4-67,R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═H, Y=i-C₃H₇)

Using the same procedure as described in the preparative method of compound 4-65, except for using 4-57 and 2 equivlent isopropylamine as starting material to obtain 4.4 mg of the title compound 4-67 in 56% yield as yellow powder, m. p. 161-162° C.

¹H-NMR (500 MHz, DMSO-d₆, ppm): 7.014 (t, 1H, J=3.0 Hz, 1.5 Hz, 5-H_(pyrrole)), 6.659 (d, 1H, J=10.0 Hz, 8-H), 6.156 (t, 1H, J=3.0 Hz, 3.5 Hz, 4-H_(pyrrole)), 5.920 (s, 1H, 3-H), 5.884 (dd, 1H, J=2.0 Hz, 3.5 Hz, 3-H_(pyrrole)), 5.703 (d, 1H, J=10.0 Hz, 7-H), 3.784 (sept, 1H, J=7.0 Hz, CH), 2.869 (m, 2H, 4-CH ₂CH₂CH₃), 1.605 (m, 2H, 4-CH₂CH ₂CH₃), 1.477, 1.453 (2s, 6H, 6-CH₃), 1.278 (d, 3H, J=7.0 Hz, CH₃), 1.228 (d, 3H, J=7.0 Hz, CH₃), 0.988 (t, 3H, J=7.5 Hz, 4-CH₂CH₂CH ₃); ¹³C-NMR (125 MHz, DMSO-d₆, ppm): 159, 157, 155, 154, 151, 127, 120, 117, 116, 110, 109, 107, 105, 102, 102, 77, 47, 37, 27, 27, 23, 23, 23, 13.

ESI-MS (m/z): 394.2 [M+H]⁺ (MW=393.49);

HRESIMS obsd. m/z 394.2021, calcd. for C₂₇H₂₈NO₄ ⁺ 394.2018.

Example 68 5-hydroxy-6-(1′-(2-pyridyl)methylene-1′H-pyrrolyl-2′-ene)-2,2-dimethyl-10-n-propyl-2H-benzo-[2,3-f]-pyranyl-8-one (4-68, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-65, except for using 4-57 and 2 equivlent 2-aminomethylpyridine as starting material to obtain 4.3 mg of the title compound 4-68 in 49% yield as off-yellow powder, m. p. 171-173° C. ¹H-NMR (300 MHz, DMSO-d₆, ppm): 8.308 (m, 1H, Ar—H), 7.573 (dt, 1H, J=1.8 Hz, 7.8 Hz, Ar—H), 7.140 (m, 1H, Ar—H), 6.940 (t, 1H, J=2.4 Hz, 5-H_(pyrrole)), 6.892 (m, 1H, Ar—H), 6.629 (d, 1H, J=9.9 Hz, 8-H), 6.177 (t, 1H, J=3.0 Hz, 4-H_(pyrrole)), 6.022 (dd, 1H, J=1.8 Hz, 3.6 Hz, 3-H_(pyrrole)), 5.832 (s, 1H, 3-H), 5.671 (d, 1H, J=9.9 Hz, 7-H), 4.941 (s, 2H, CH₂), 2.806 (m, 2H, 4-CH ₂CH₂CH₃), 1.552 (m, 2H, 4-CH₂CH ₂CH₃), 1.438 (s, 6H, 6-CH₃), 0.967 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 443.1 [M+H]⁺ (MW=442.52);

HRESIMS obsd. m/z 443.1973, calcd. for C₂₇H₂₇N₂O₄ ⁺ 443.19708.

Example 69 5-hydroxy-6-[1′-(2-furanyl)methylene-1′H-pyrrolyl-2′-ene]-2,2-dimethyl-10-n-propyl-2H-benzo[2,3-f]-pyranyl-8-one (4-69, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═H)

Using the same procedure as described in the preparative method of compound 4-65, except for using 0.02 mmol compound 4-57 and 2 equivlent 2-aminomethylfuran as starting material to obtain 5.2 mg of the title compound 4-69 in 61% yield as off-white powder, m. p. 157-159° C. ¹H-NMR (500 MHz, DMSO-d₆, ppm): 7.397 (d, 1H, J=1.0 Hz, CH), 6.884 (dd, 1H, J=1.5 Hz, 2.5 Hz, CH), 6.673 (d, 1H, J=10.0 Hz, 8-H), 6.219 (dd, 1H, J=1.5 Hz, 3.5 Hz, CH), 6.120 (t, 1H, J=3.5 Hz, CH), 5.984 (dd, 1H, J=1.5 Hz, 3.5 Hz, CH), 5.945 (d, 1H, J=3.5 Hz, CH), 5.900 (s, 1H, 3-H), 5.721 (d, 1H, J=10.0 Hz, 7-H), 4.789 (q, 2H, J=16.0 Hz, 18.5 Hz, CH₂), 2.871 (m, 2H, 4-CH ₂CH₂CH₃), 1.614 (m, 2H, 4-CH₂CH ₂CH₃), 1.483, 1.464 (2s, 6H, 6-CH₃), 0.992 (t, 3H, J=7.5 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 432.1 [M+H]⁺ (MW=431.49);

HRESIMS obsd. m/z 432.1810, calcd. for C₂₆H₂₆NO₅ ⁺ 432.18109.

Example 70

6,6,-dimethyl-4-propyl-10,11-cis-cyclopropyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]tripyranyl-2,12-dione (4-70, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═CH₂)

The title compound 4-70 can be synthesized in two methods:

Method 1:

(1) benzo[1,2-b:3,4-b′]dipyranyl-5-hydroxyl-8,9-cis-cyclopropyl-4-n-propyl-2,10-dione (5a-70, R₁=n-C₃H₇, R₂H, R₃═R₄═CH₂)

20 mg (excess) NaH was added into the solution of 38 mg compound 5a-57 in 10 ml absolute anhydrous THF and the reaction mixture was stirred for 48 hours at room temperature. After filtration, the resulted yellowish powder was dissolved in 2 ml methonal and then acidified with 1M hydrochloric acid. Extracted 3 times with EtOAc, the combined organic phase was dried, filtrated and purified through chromatography on silica gel eluting with petroleum-EtOAC (2:1) to afford compound 5a-70 in 69% yield as white powder. ¹H NMR (300M Hz, DMSO-d₆, ppm): 11.708 (s, 1H, OH), 6.283 (S, 1H, Ph-H), 6.050 (s, 1H, 3-H), 4.731 (m, 1H, 8-H), 2.860 (t, 2H, J=7.8 Hz, 4-CH2CH2CH3), 2.118 (m, 1H, 9-H), 1.615-1.443 (m, 4H, 11-CH2,CH2CH2CH3), 0.923 (t, 3H, J=7.5 Hz, 4-CH2CH2CH3);

ESI-MS (m/z): 287.24 [M+H]⁺ (MW=286.28); HRESIMS obsd. m/z 287.0914, calcd. for C₁₆H₁₅O₅ ⁺ 287.0914.

(2) 6,6,-dimethyl-4-n-propyl-10,11-cis-cyclopropyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]tripyranyl-2,12-dione (4-70, R₁=n-C₃H₇, R₅═R₆═CH₃, R₂═R₄═CH₂)

Using the same procedure as described in the preparative method of compound 4-1, except for using 19 mg (0.05 mmol) compound 5a-70 and 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain 11 mg of the title compound 4-70 in 48% yield as off-white powder, m. p. 113-115° C. ¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.554 (d, 1H, J=9.9 Hz, 8-H), 6.123 (s, 1H, 3-H), 5.800 (d, 1H, J=9.9 Hz, 7-H), 4.862 (m, 1H, 10-H), 2.844 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.181 (m, 1H, 11-CH), 1.568 (m, 4H, 13-CH₂, 4-CH₂CH ₂CH₃), 1.490, 1.456 (2s, 6H, 6-CH₃), 0.967 (t, 3H, J=7.5 Hz, 4-CH₂CH₂CH ₃); ESI-MS (m/z): 353.1 [M+H]⁺ (MW=352.39); HRESIMS obsd. m/z 353.1392, calcd. for C₂₁H₂₁O₅ ⁺ 353.1389.

Method 2:

Using the method for synthesizing compound 4-67 (or 4-68, 4-69), compound 4-70 can be obtained simutaiously in 15-20% yield as yellow powder, m. p. 113-115° C. ¹H-NMR (500 MHz, DMSO-d₆, ppm): 6.557 (d, 1H, J=10.0 Hz, 8-H), 6.125 (s, 1H, 3-H), 5.801 (d, 1H, J=10.0 Hz, 7-H), 4.866 (m, 1H, 10-H), 2.847 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.182 (dt, 1H, J=6.5 Hz, 9.0 Hz, 11-CH), 1.570 (m, 4H, 13-CH₂, 4-CH₂CH ₂CH₃), 1.492, 1.458 (2s, 6H, 6-CH₃), 0.969 (t, 3H, J=7.5 Hz, 4-CH₂CH₂CH ₃); ESI-MS (m/z): 353.1 [M+H]⁺ (MW=352.39); HRESIMS obsd. m/z 353.1392, calcd. for C₂₁H₂₁O₅ ⁺ 353.1389.

Example 71 6,6,10-trimethyl-4-(3,3′,3″-trifluoromethyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-71)

(1) 4-(3,3′,3″-trifluoro)-n-propyl-5,7-dihydroxy-coumarin (6-71)

Using the same procedure as described in the preparative method of compound (6-1), except for using phloroglucinol and Ethyl 4-trifluorobutyryl acetate as starting material to obtain the title compound in 78% yield as a brown yellow powder. m. p. 205-207° C.;

¹H-NMR (300 MHz, DMSO-d₆, ppm): 10.821 (s, 1H, OH), 10.366 (s, 1H, OH), 6.277 (d, 1H, J=2.4 Hz, 8-H), 6.193 (d, 1H, J=2.4 Hz, 6-H), 5.970 (s, 1H, 3-H), 3.096 (t, 2H, J=7.8 Hz, 4-CH ₂CH₂CF₃), 2.572 (m, 2H, 4-CH₂CH ₂CF₃);

¹⁹F-NMR (400 MHz, DMSO-d₆, ppm): −65.129 (t, J=11.2 Hz);

ESI-MS (m/z): 273.5 [M−H]⁻ (MW=274.20);

HRESIMS obsd. m/z 273.0400, calcd. for C₁₂H₈F₃O₄ ⁻ 273.03746.

(2) benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-((3,3′,3″-trifluoro)-n-propyl)-2,10-dione (5a-71)

Using the same procedure as described in the preparative method of compound 5a-1, except for using compound 4-(γ-trifluoropropyl)-5,7-dihydroxy-coumarin (6-71) and crotonic acid as starting material to obtain of the title compound 5a-71 in 77% yield as a brown yellow powder, m. p. 127-129° C. ¹H-NMR (300 MHz, DMSO-d₆, ppm): 12.676 (s, 1H, OH, 6.269 (s, 1H, 6-H), 5.987 (s, 1H, 3-H), 4.631 (m, 1H, 8-H), 3.135 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CF₃), 2.637 (m, 2H, 9-CH₂), 2.584 (m, 2H, 4-CH₂CH ₂CF₃), 1.385 (d, 3H, J=6.0 Hz, 8-CH₃);

¹⁹F-NMR (400 MHz, DMSO-d₆, ppm): −64.971 (t, J=11.2 Hz);

ESI-MS (m/z): 341.2 [M−H]⁻ (MW=342.27);

HRESIMS obsd. m/z 341.0643, calcd. for C₁₆H₁₂F₃O₅ ⁻ 341.06368.

(3) 6,6,10-trimethyl-4-(3,3′, 3″-trifluoromethyl)-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyran yl-2,12-dione (4-71, R₁=n-C₂H₄CF₃, R₂═H, R₃═R₅═R₆═CH₃, R₄═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-71 and 1,1-diethoxyl-3-methyl-2-butene as starting material to obtain the title compound in 72% yield as brown-yellow powder, m. p. 133-134° C.

¹H-NMR (500 MHz, DMSO-d₆, ppm): 6.602 (d, 1H, J=10.0 Hz, 8-H), 6.266 (s, 1H, 3-H), 5.810 (d, 1H, J=10.0 Hz, 7-H), 4.723 (m, 1H, 10-H), 3.164 (m, 2H, 4-CH ₂CH₂CF₃), 2.661 (m, 2H, 11-CH₂), 2.568 (m, 2H, 4-CH₂CH ₂CF₃), 1.497, 1.464 (2s, 6H, 6-CH₃), 1.449 (d, 3H, J=6.0 Hz, 10-CH₃);

¹⁹F-NMR (400 MHz, DMSO-d₆, ppm): −64.764 (t, J=11.2 Hz);

ESI-MS (m/z): 409.1 [M+H]⁺ (MW=408.38);

HRESIMS obsd. m/z 409.1271, calcd. for C₂₁H₂₀F³O₅ ⁺ 409.12628.

Example 72 4-(3,3′,3″-trifluoro-n-propyl)-6-propenyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-72, R₁=n-C₂H₄CF₃, R₂═H, R₃═CH₃, R₅═C₃H₅, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-71 and 1,1-diethoxyl-2,4-hexadiene as starting material to obtain the title compound 4-72 in 56% yield as brown-yellow powder, m. p. 147-149° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 6.744 (d, 1H, J=12.3 Hz, CH), 6.511 (m, 1H, CH), 6.207 (s, 1H, 3-H), 6.027 (m, 1H, CH), 5.845 (m, 1H, CH), 5.596 (m, 1H, CH), 4.710 (m, 1H, 10-H), 3.100 (t, 2H, J=7.6 Hz, 4-CH ₂CH₂CF₃), 2.655 (m, 2H, 11-CH₂), 2.015 (m, 2H, 4-CH₂CH ₂CF₃), 1.681 (d, 3H, J=6.4 Hz, CH₃), 1.388 (dd, 3H, J=4.4 Hz, 6.0 Hz, 10-CH₃);

ESI-MS (m/z): 421.1 [M+H]⁺ (MW=420.39);

HRESIMS obsd. m/z 421.1263, calcd. for C₂₂H₂₀F₃O₅ ⁺ 421.12628.

Example 73 4-(3,3′,3″-trifluoro-n-propyl)-6-n-butyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-73, R₁=n-C₂H₄CF₃, R₂═H, R₃═CH₃, R₅═C₄H₉, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-71 and 1,1-diethoxyl-2-heptene as starting material to obtain the title compound 4-73 in 74% yield as yellow powder, m. p. 129-130° C.

¹H-NMR (500 MHz, DMSO-d₆, ppm): 6.658 (dt, 1H, J=2.0 Hz, 10.0 Hz, 8-H), 6.241 (d, 1H, J=3.0 Hz, 3-H), 5.847 (dq, 1H, J=3.5 Hz, 10.0 Hz, 7-H), 5.155 (m, 1H, 6-H), 4.717 (m, 1H, 10-H), 3.189 (m, 2H, CH₂), 3.091 (m, 2H, 4-CH ₂CH₂CF₃), 2.657 (m, 2H, 11-CH₂), 1.997 (m, 2H, 4-CH₂CH ₂CF₃), 1.791 (m, 2H, CH₂), 1.446 (d, 3H, J=6.5 Hz, 10-CH₃), 1.370 (m, 2H, CH₂), 0.870 (t, 3H, J=7.5 Hz, CH₃);

ESI-MS (m/z): 437.1 [M+H]⁺ (MW=436.43);

HRESIMS obsd. m/z 437.1577, calcd. for C₂₃H₂₄F³O₅ ⁺ 437.15758.

Example 74 4-(3,3′, 3″-trifluoro-n-propyl)-6-phenyl-O-methyl-2H,6H, 2H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-74, R₁=n-C₂H₄CF₃, R₂═H, R₃═CH₃, R₅=Ph, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-71 and 1,1-diethoxyl-3-pheny-propene as starting material to obtain the title compound 4-74 in 58% yield as yellowish powder, m. p. 171-173° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 7.411 (m, 5H, 6-Ph), 6.861 (dt, 1H, J=2.0 Hz, 10.0 Hz, 8-H), 6.283 (m, 1H, 6-H), 6.186 (d, 1H, J=2.0 Hz, 3-H), 5.970 (dq, 1H, J=4.5 Hz, 10.0 Hz, 7-H), 4.766 (m, 1H, 10-H), 2.931 (m, 2H, 4-CH ₂CH₂CF₃), 2.703 (m, 2H, 11-CH₂), 1.978 (m, 2H, 4-CH₂CH ₂CF₃), 1.479 (dd, 3H, J=5.5 Hz, 7.5 Hz, 10-CH₃);

ESI-MS (m/z): 457.1 [M+H]⁺ (MW=456.42);

HRESIMS obsd. m/z 457.1264, calcd. for C₂₅H₂₀F³O₅ ⁺ 457.12628.

Example 75 6,11-dimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-75, R₁=n-C₃H₇, R₂═H, R₄═R₅═CH₃, R₃═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-51 and 1,1-diethoxyl-2-butene as starting material to obtain the title compound 4-75 in 79% yield as off-white powder, m. p. 135-137° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.611 (dd, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.107 (s, 1H, 3-H), 5.812 (dq, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 5.204 (m, 1H, 6-H), 4.640 (dt, 1H, J=2.1 Hz, 12.3 Hz, CH), 4.252 (dq, 1H, J=3.0 Hz, 12.3 Hz, CH), 2.829 (m, 3H, 4-CH₂, 11-CH), 1.559 (m, 2H, 4-CH₂CH ₂CH₃), 1.460 (t, 3H, J=6.6 Hz, CH₃), 1.331 (d, 3H, J=6.3 Hz, CH₃), 0.950 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 340.9 [M+H]⁺ (MW=340.38);

HRESIMS obsd m/z 341.1386, calcd for C₂₀H₂₁O₅ ⁺ 341.1389.

Example 76 4-n-propyl-6-propenyl-11-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-76, R₁=n-C₃H₇, R₂═H, R₄═CH₃, R₃═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-51 and 1,1-diethoxyl-2,4-hexadiene as starting material to obtain the title compound 4-76 in 65% yield as orange powder, m. p. 165-166° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.764 (dd, 1H, J=4.8 Hz, 12.3 Hz, CH), 6.305 (m, 1H, CH), 6.078 (s, 1H, 3-H), 5.979 (m, 1H, CH), 5.568 (m, 2H, 2CH), 4.589 (m, 2H, 10-CH₂), 2.782 (m, 3H, 4-CH ₂CH₂CH₃, 11-CH), 1.676 (m, 3H, CH₃), 1.497 (m, 2H, 4-CH₂CH ₂CH₃), 1.043 (m, 3H, CH₃), 0.874 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 366.9 [M+H]⁺ (MW=366.42);

HRESIMS obsd. m/z 367.15399, calcd. for C₂₂H₂₃O₅ ⁺ 367.15455.

Example 77 4-n-propyl-6-n-butyl-11-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-77, R₁=n-C₃H₇, R₂═H, R₄═CH₃,R₅=n-C₄H₉, R₃═R₆═H⁾

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-51 and 1,1-diethoxyl-2-heptene as starting material to obtain the title compound 4-77 in 71% yield as off-white powder, m. p. 144-145° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.630 (dd, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.098 (s, 1H, 3-H), 5.814 (dq, 1H, J=3.0 Hz, 9.9 Hz, 7-H), 5.114 (m, 1H, 6-H), 4.625 (dd, 1H, J=5.1 Hz, 11.1 Hz, CH), 4.246 (dq, 1H, J=3.01 Hz, 11.1 Hz, CH), 2.853 (m, 3H, 4-CH₂, 11-CH), 1.790 (m, 2H, 6-CH₂), 1.556 (m, 2H, 4-CH₂CH ₂CH₃), 1.341 (d, 3H, J=6.3 Hz, CH₃), 1.085 (m, 4H, CH₂), 0.947 (m, 6H, CH₃);

ESI-MS (m/z): 382.9 [M+H]⁺ (MW=382.46);

HRESIMS obsd. m/z 383.18972, calcd. for C₂₃H₂₇O₅ ⁺ 383.18585.

Example 78 4-n-propyl-6-phenyl-11-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-78, R₁=n-C₃H₇, R₂═H, R₄═CH₃,R₅=Ph, R₃═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-51 and 1,1-diethoxyl-3-phenyl-propene as starting material to obtain the title compound 4-78 in 70% yield as off-white powder, m. p. 187-189° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.426 (m, 5H, 6-Ph), 6.816 (dq, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.223 (dq, 1H, J=1.8 Hz, 8.7 Hz, 6-H), 6.038 (s, 1H, 3-H), 5.923 (dq, 1H, J=1.8 Hz, 9.9 Hz, 7-H), 4.668 (dq, 1H, J=5.1 Hz, 11.1 Hz, CH), 4.294 (dt, 1H, J=1.2 Hz, 11.1 Hz, CH), 2.894 (m, 1H, 11-CH), 2.640 (m, 2H, 4-CH₂), 1.312 (m, 2H, 4-CH₂CH ₂CH₃), 1.066 (d, 3H, J=6.9 Hz, 11-CH₃), 0.621 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 402.9 [M+H]⁺ (MW=402.45);

HRESIMS obsd. m/z 403.1541, calcd. for C₂₅H₂₃O₅ ⁺ 403.15455.

Example 79 6,10-dimethyl-4-ethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione

(4-79, R₁═C₂H₅, R₂═H, R₃═R₅═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-9 and 1,1-diethoxyl-2-butene as starting material to obtain the title compound 4-79 in 59% yield as off-white powder, m. p. 133-134° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.625 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.101 (s, 1H, 3-H), 5.818 (dt, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 5.514 (m, 1H, 6-H), 4.716 (m, 1H, 10-H), 2.997 (m, 2H, 4-CH ₂CH₃), 2.667 (m, 2H, 11-CH₂), 1.441 (d, 3H, J=6.0 Hz, 6-CH₃), 1.435 (d, 3H, J=6.3 Hz, 10-CH₃), 1.174 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 326.9 [M+H]⁺ (MW=326.35);

Anal. Calcd. for C₁₉H₁₈O₅. 2/3H₂O: C, 67.44; H, 5.76. Found: C, 67.45; H, 6.24.

Example 80 6,10-dimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione

(4-80, R₁=n-C₃H₇, R₂═H, R₃═R₅═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-11 and 1,1-diethoxyl-2-butene as starting material to obtain the title compound 4-80 in 62% yield as off-white powder, m. p. 125-127° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.628 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.107 (s, 1H, 3-H), 5.813 (dt, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 5.217 (m, 1H, 6-H), 4.726 (m, 1H, 10-H), 2.820 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.659 (m, 2H, 11-CH₂), 1.558 (m, 2H, 4-CH₂CH ₂CH₃), 1.478 (d, 3H, J=6.6 Hz, 6-CH₃), 1.440 (d, 3H, J=6.3 Hz, 10-CH₃), 0.951 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 340.9 [M+H]⁺ (MW=340.38);

Anal. Calcd. for C₂₀H₂₀O₅.1/2H₂O: C, 68.75; H, 6.06. Found: C, 68.93; H, 6.50.

Example 81 6,10-dimethyl-4-n-propyl-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-81, R₁=n-C₃H₇, R₂═Cl, R₃═R₅═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-20 and 1,1-diethoxyl-2-butene as starting material to obtain the title compound 4-81 in 64% yield as off-white powder, m. p. 129-131° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.646 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 5.856 (dt, 1H, J=3.0 Hz, 9.9 Hz, 7-H), 5.240 (m, 1H, 6-H), 4.738 (m, 1H, 10-H), 3.097 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.693 (m, 2H, 11-CH₂), 1.573 (m, 2H, 4-CH₂CH ₂CH₃), 1.516 (d, 3H, J=6.6 Hz, 6-CH₃), 1.448 (d, 3H, J=6.3 Hz, 10-CH₃), 1.023 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 374.9 M⁺ (MW=374.82);

Anal. Calcd. for C₂₀H₁₉ClO₅: C, 64.09; H, 5.11. Found: C, 63.82; H, 5.25.

Example 82 6,10-dimethyl-4-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-82, R₁=n-C₄H₉, R₂═H, R₃═R₅═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-36 and 1,1-diethoxyl-2-butene as starting material to obtain the title compound 4-82 in 61% yield as yellowish powder, m. p. 128-129° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.634 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 6.109 (s, 1H, 3-H), 5.818 (dt, 1H, J=3.0 Hz, 9.9 Hz, 7-H), 5.198 (m, 1H, 6-H), 4.716 (m, 1H, 10-H), 2.843 (m, 2H, 4-CH ₂CH₂CH₂CH₃), 2.657 (m, 2H, 11-CH₂), 1.530 (m, 2H, 4-CH₂CH ₂CH₂CH₃), 1.470 (d, 3H, J=6.6 Hz, 6-CH₃), 1.440 (d, 3H, J=6.3 Hz, 10-CH₃), 1.384 (m, 2H, 4-CH₂CH₂CH ₂CH₃), 0.904 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH₂CH ₃);

ESI-MS (m/z): 354.9 [M+H]⁺ (MW=354.41);

Anal. Calcd. for C₂₁H₂₂O₅.1/4H₂O: C, 70.28; H, 6.32. Found: C, 70.33; H, 6.29.

Example 83 6,10-dimethyl-4-ethyl-3-fluoro-2H, H, 12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-83, R₁═C₂H₅, R₂═F, R₃═R₅═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-10 and 1,1-diethoxyl-2-butene as starting material to obtain the title compound 4-83 in 65% yield as off-white powder, m. p. 141-142° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.639 (dt, 1H, J=1.8 Hz, 9.9 Hz, 8-H), 5.852 (dt, 1H, J=3.3 Hz, 9.9 Hz, 7-H), 5.547 (m, 1H, 6-H), 4.715 (m, 1H, 10-H), 2.968 (m, 2H, 4-CH ₂CH₃), 2.677 (m, 2H, 11-CH₂), 1.483 (d, 3H, J=6.6 Hz, 6-CH₃), 1.444 (d, 3H, J=6.3 Hz, 10-CH₃), 1.198 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 344.9 [M+H]⁺ (MW=344.34);

Anal. Calcd. for C₁₉H₁₇FO₅.1/2H₂O: C, 64.58; H, 5.13. Found: C, 64.51; H, 5.39.

Example 84 6,10-dimethyl-4-n-propyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-84, R₁=n-C₃H₇, R₂═F, R₃═R₅═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-31 and 1,1-diethoxyl-2-butene as starting material to obtain the title compound 4-84 in 66% yield as off-white powder, m. p. 150-153° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.636 (dt, 1H, J=2.1 Hz, 9.9 Hz, 8-H), 5.844 (dt, 1H, J=3.3 Hz, 7-H), 5.190 (m, 1H, 6-H), 4.713 (m, 1H, 10-H), 2.902 (m, 2H, 4-CH ₂CH₂CH₃), 2.676 (m, 2H, 11-CH₂), 1.586 (m, 2H, 4-CH₂CH ₂CH₃), 1.483 (d, 3H, J=6.6 Hz, 6-CH₃), 1.442 (d, 3H, J=6.3 Hz, 10-CH₃), 0.970 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 358.9 [M+H]⁺ (MW=358.37);

HRESIMS obsd. m/z 359.1291, calcd. for C₂₀H₂₀FO₅ ⁺ 359.12947.

Example 85 4-n-propyl-6-propenyl-1-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-85, R₁=n-C₃H₇, R₃═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-11 and 1,1-diethoxyl-2,4-hexdiene as starting material to obtain the title compound 4-85 in 63% yield as orange powder, m. p. 136-138° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.652 (dq, 1H, J=1.5 Hz, 9.9 Hz, 8-H), 6.074 (s, 1H, 3-H), 5.904 (m, 1H, CH), 5.805 (dd, 1H, J=3.9 Hz, 9.9 Hz, 7-H), 5.702 (dq, 1H, J=6.0 Hz, 13.5 Hz, CH), 5.506 (m, 1H, 6-H), 4.715 (m, 1H, 10-H), 2.761 (m, 2H, 4-CH ₂CH₂CH₃), 2.650 (m, 2H, 11-CH₂), 1.682 (dt, 3H, J=1.21 Hz, 6.0 Hz, CH₃), 1.505 (m, 2H, 4-CH₂CH ₂CH₃), 1.440 (dd, 3H, J=2.7 Hz, 6.3 Hz, 10-CH₃), 0.901 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 366.9 [M+H]⁺ (MW=366.42);

Anal. Calcd. for C₂₂H₂₂O₅.H₂O: C, 68.74; H, 6.29. Found: C, 68.53; H, 6.22.

Example 86 4-n-propyl-6-propenyl-3-chloro-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-86, R₁=n-C₃H₇, R₂═Cl, R₃═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-20 and 1,1-diethoxyl-2,4-hexdiene as starting material to obtain the title compound 4-86 in 58% yield as off-white powder, m. p. 142-144° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.690 (dq, 11, J=1.2 Hz, 9.9 Hz, CH), 5.931 (m, 1H, CH), 5.854 (m, 1H, CH), 5.738 (m, 1H, CH), 5.580 (m, 1H, CH), 4.750 (m, 1H, 10-H), 3.063 (m, 2H, 4-CH ₂CH₂CH₃), 2.671 (m, 2H, 11-CH₂), 1.690 (dt, 3H, J=1.5 Hz, 6.6 Hz, CH₃), 1.528 (m, 2H, 4-CH₂CH ₂CH₃), 1.452 (dd, 3H, J=3.0 Hz, 6.3 Hz, 10-CH₃), 0.984 (dt, 3H, J=3.6 Hz, 7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 400.9 M⁺ (MW=400.86);

HRESIMS obsd. m/z 401.1163, calcd. for C₂₂H₂₂ClO₅ ⁺ 401.11557.

Example 87 4-ethyl-6-propenyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-d ione (4-87, R₁═C₂H₅, R₂═H R₃═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-9 and 1,1-diethoxyl-2,4-hexdiene as starting material to obtain the title compound 4-87 in 67% yield as orange powder, m. p. 153-155° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.762 (dd, 1H, J=3.9 Hz, 12.6 Hz, CH), 6.340 (m, 1H, CH), 6.069 (s, 1H, 3-H), 5.823 (m, 1H, CH), 5.596 (m, 2H, 2CH), 4.601 (m, 1H, 10-H), 2.858 (m, 2H, 4-CH ₂CH₃), 2.606 (m, 2H, 11-CH₂), 1.677 (m, 3H, CH₃), 1.340 (m, 3H, CH₃), 1.198 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 352.9 [M+H]⁺ (MW=352.39);

Anal. Calcd. for C₂₁H₂₀O₅.2H₂O: C, 64.94; H, 6.23. Found: C, 65.15; H, 6.18.

HRESIMS obsd. m/z 353.1398, calcd. for C₂₁H₂₁O₅ ⁺ 353.1389.

Example 88 4-ethyl-6-propenyl-3-fluoro-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyran yl-2,12-dione (4-88, R₁═C₂H₅, R₂═F, R₃═CH₃, R₄═R₆═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-10 and 1,1-diethoxyl-2,4-hexdiiene as starting material to obtain the title compound 4-88 in 66% yield as yellow powder, m. p. 158-161° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.773 (dd, 1H, 3.3 Hz, 12.3 Hz, CH), 6.361 (m, 1H, CH), 6.044 (m, 1H, CH), 5.598 (m, 2H, 2CH), 4.648 (m, 1H, 10-H), 2.940 (m, 2H, 4-CH ₂CH₃), 2.620 (m, 2H, 11-CH₂), 1.701 (m, 3H, CH₃), 1.375 (d, 3H, J=6.3 Hz, 10-CH₃), 1.129 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 370.9 [M+H]⁺ (MW=370.38);

Anal. Calcd. for C₂₁H₁₉FO₅.5/3H₂O: C, 62.99; H, 5.62. Found: C, 62.83; H, 5.78.

Example 89 4-ethyl-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione (4-89, R₁═C₂H₅, R₂═H, R₃═CH₃, R₄═R₅═R₆═H, R₇═CH₃, R₈═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-9 and 1,1-diethoxyl-2-methylpropene as starting material to obtain the title compound 4-89 in 49% yield as white powder, m. p. 121-123° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.400 (q, 1H, J=1.8 Hz, 8-H), 6.107 (s, 1H, 3-H), 4.852 (s, 2H, 6-CH₂), 4.697 (m, 1H, 10-H), 2.875 (q, 2H, J=7.2 Hz, 4-CH ₂CH₃), 2.697 (m, 2H, 11-CH₂), 1.827 (d, 3H, J=1.8 Hz, 7-CH₃), 1.442 (d, 3H, J=6.3 Hz, 10-CH₃), 1.145 (d, 3H, J=7.2 Hz, 4-CH₂CH₃);

ESI-MS (m/z): 326.9 [M+H]⁺ (MW=326.35);

Anal. Calcd. for C₁₉H₁₈O₅.3/4H₂O: C, 67.15; H, 5.78. Found: C, 67.21; H, 5.58.

Example 90 4-n-propyl-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-90, R₁=n-C₃H₇, R₂═H, R₃═CH₃, R₄═R₅═R₆=H, R₇═CH₃, R₈═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-11 and 1,1-diethoxyl-2-methylpropene as starting material to obtain the title compound 4-90 in 53% yield as white powder, m. p. 127-128° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.401 (m, 1H, 8-H), 6.104 (s, 1H, 3-H), 4.851 (s, 2H, 6-CH₂), 4.697 (m, 1H, 10-H), 2.799 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.659 (m, 2H, 11-CH₂), 1.828 (s, 3H, 7-CH₃), 1.546 (m, 2H, 4-CH₂CH ₂CH₃), 1.441 (d, 3H, J=6.3 Hz, 10-CH₃), 0.941 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (n2/z): 340.9 [M+H]⁺ (MW=340.38);

Anal. Calcd. for C₂₀H₂₀O₅.3/4H₂O: C, 67.88; H, 6.12. Found: C, 67.96; H, 6.44.

Example 91 4-n-propyl-3-chloro-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-91, R₁=n-C₃H₇, R₂═Cl, R₃═CH₃, R₄═R₅═R₆═H, R₇═CH₃, R₈=H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-20 and 1,1-diethoxyl-2-methylpropene as starting material to obtain the title compound 4-91 in 51% yield as white powder, m. p. 129-131° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.415 (q, 1H, J=1.5 Hz, 8-H), 4.882 (s, 2H, 6-CH₂), 4.719 (m, 1H, 10-H), 3.075 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.678 (m, 2H, 11-CH₂), 1.844 (d, 3H, J=1.5 Hz, 7-CH₃), 1.556 (m, 2H, 4-CH₂CH ₂CH₃), 1.448 (d, 3H, J=6.3 Hz, 10-CH₃), 1.009 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 374.9 M⁺ (MW=374.82);

Anal. Calcd. for C₂₀H₁₉ClO₅.1/2H₂O: C, 62.58; H, 5.25. Found: C, 62.56; H, 5.72.

Example 92 4-n-propyl-3-fluoro-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-92, R₁═C₂H₅, R₂═F, R₃═CH₃, R₄═R₅═R₆═H, R₇═CH₃, R₈═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-31 and 1,1-diethoxyl-2-methylpropene as starting material to obtain the title compound 4-92 in 47% yield as brown powder, m. p. 122-124° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.408 (s, 1H, 8-H), 4.863 (s, 2H, 6-CH₂), 4.697 (m, 1H, 10-H), 2.897 (m, 2H, 4-CH ₂CH₂CH₃), 2.671 (m, 2H, 11-CH₂), 1.836 (s, 3H, 7-CH₃), 1.570 (m, 2H, 4-CH₂CH ₂CH₃), 1.443 (d, 311, J=6.0 Hz, 10-CH₃), 0.958 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 358.9 [M+H]⁺ (MW=358.37);

Anal. Calcd. for C₂₀H₁₉FO₅.2/3H₂O: C, 64.86; H, 5.53. Found: C, 64.72; H, 5.96.

Example 93 4-ethyl-3-fluoro-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-93, R₁═C₂H₅, R₂═F, R₃═CH₃, R₄═R₅═R₆═H, R₇═CH₃, R₈═H)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-10 and 1,1-diethoxyl-2-methylpropene as starting material to obtain the title compound 4-93 in 49% yield as yellowish powder, m. p. 118-120° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.382 (d, 1H, J=1.5 Hz, 8-H), 4.857 (s, 2H, 6-CH₂), 4.668 (m, 1H, 10-H), 2.899 (q, 2H, J=7.2 Hz, 4-CH ₂CH₃), 2.687 (m, 2H, 11-CH₂), 1.828 (s, 3H, 7-CH₃), 1.442 (d, 3H, J=6.0 Hz, 10-CH₃), 1.149 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃);

ESI-MS (m/z): 344.9 [M+H]⁺ (MW=344.34);

And the title compounds 4-94, 4-95, 4-96 were simutaiously obtained respectively when the compounds 4-89, 4-90 and 4-91 were produced in this method.

Example 94 8-ethyoxyl-7,10-dimethyl-4-ethyl-7,8,10,11-tetrahydro-6H-benzo[2,3-f;2′,3′-h]-tripyran yl-2,12-dione (4-94, R₁═C₂H₅, R₂═H, R₃═CH₃, R₄═R₅═R₆═H, R₇═CH₃, R₈═OC₂H₅)

It is white powder, yield 19%, m. p. 174-176° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.106 (s, 1H, 3-H), 5.169 (dd, 1H, J=5.41 Hz, 4.8 Hz, 8-H), 4.703 (m, 1H, 10-H), 3.850 (dq, 1H, J=7.2 Hz, 14.1 Hz, 6-CH), 3.701 (dq, 1H, J=2.7 Hz, 14.1 Hz, 6-CH), 3.013 (sex, 1H, J=7.2 Hz, 14.7 Hz, OCH ₂CH₃), 2.898 (q, 2H, J=7.2 Hz, 4-CH ₂CH₃), 2.691 (m, 2H, 11-CH₂), 2.324 (dt, 1H, J=6.9 Hz, 14.7 Hz, OCH ₂CH₃), 2.047 (m, 1H, 7-H), 1.434 (d, 3H, J=6.3 Hz, 10-CH₃), 1.173 (dd, 3H, J=6.9 Hz, 7.2 Hz, OCH₂CH ₃), 1.148 (t, 3H, J=7.2 Hz, 4-CH₂CH ₃), 0.982 (d, 3H, J=6.9 Hz, 7-CH₃);

ESI-MS (n2/z): 372.9 [M+H]⁺ (MW=372.42);

Anal. Calcd. for C₂₁H₂₄O₆.1/3H₂O: C, 66.65; H, 6.56. Found: C, 66.43; H, 6.33.

Example 95 8-ethyoxyl-7,10-dimethyl-4-n-propyl-7,8,10,11-tetrahydro-6H-benzo[2,3-f;2′,3‘-h’ ]-trip yranyl-2,12-dione (4-95, R₁=n-C₃H₇, R₂═H, R₃═CH₃, R₄═R₅═R₆═H, R₇═CH₃, R₈═OC₂H₅)

It is white powder, yield 26%, m. p. 198-201° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 6.097 (s, 1H, 3-H), 5.154 (dd, 1H, J=5.4 Hz, 8-H), 4.703 (m, 1H, 10-H), 3.864 (dq, 1H, J=7.2 Hz, 14.1 Hz, 6-CH), 3.709 (dq, 1H, J=2.7 Hz, 14.1 Hz, 6-CH), 2.956 (dd, 1H, J=7.2 Hz, 13.8 Hz, OCH ₂CH₃), 2.866 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.783 (dd, 1H, J=8.1 Hz, 14.1 Hz, 11-CH), 2.646 (dd, 1H, J=3.9 Hz, 14.1 Hz, 11-CH), 2.301 (dd, 1H, J=6.9 Hz, 13.8 Hz, OCH ₂CH₃), 2.035 (qu, 1H, J=5.7 Hz, 6.3 Hz, 7-H), 1.568 (sex, 2H, J=7.5 Hz, 7.2 Hz, 4-CH₂CH ₂CH₃), 1.433 (d, 3H, J=6.3 Hz, 10-CH₃), 1.162 (t, 3H, J=7.2 Hz, OCH₂CH ₃), 0.954 (d, 3H, J=5.7 Hz, 7-CH₃), 0.944 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH₃);

ESI-MS (m/z): 386.9 [M+H]⁺ (MW=386.45);

Anal. Calcd. for C₂₂H₂₆O₆.1/4H₂O: C, 67.59; H, 6.83. Found: C, 67.48; H, 6.68.

Example 96 8-ethoxyl-7,10-dimethyl-4-n-propyl-3-chloro-7,8,10,11-tetrahydro-6H-benzo[2,3-f;2′,3′-h]-tripyranyl-2,12-dione (4-96, R₁=n-C₃H₇, R₂═Cl, R₃═CH₃, R₄═R₅═R₆═H, R₇═CH₃, R₈═OC₂H₅)

It is yellow powder, yield 21%, m. p. 187-189° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 5.223 (dd, 1H, J=8.1 Hz, 4.8 Hz, 8-H), 4.724 (m, 1H, 10-H), 3.846 (dq, 1H, J=2.7 Hz, 7.2 Hz, 6-CH), 3.732 (dq, 1H, J=3.3 Hz, 7.2 Hz, 6-CH), 3.176 (m, 2H, 4-CH ₂CH₂CH₃), 2.777 (m, 1H, OCH₂CH₃), 2.680 (m, 2H, 11-CH₂), 2.354 (dt, 1H, J=6.0 Hz, 16.8 Hz, OCH ₂CH₃), 2.090 (m, 1H, 7-H), 1.576 (m, 2H, 4-CH₂CH ₂CH₃), 1.440 (d, 3H, J=6.3 Hz, 10-CH₃), 1.153 (q, 3H, J=7.2 Hz, OCH₂CH ₃), 1.007 (t, 3H, J=7.5 Hz, 4-CH₂CH₂CH ₃), 0.957 (t, 3H, J=6.6 Hz, 7-CH₃);

ESI-MS (m/z): 420.9 M⁺ (MW=420.89);

Anal. Calcd. for C₂₂H₂₅ClO₆: C, 62.78; H, 5.99. Found: C, 62.90; H, 5.96.

Example 97 4-n-propyl-6-(o-nitrophenyl)-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-97, R₁=n-C₃H₇, R₂═H, R₃═CH₃, R₄═R₆═H, R₅=Ph-NO₂)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-11 and o-nitrophenyl(ethyl)acetal as starting material to obtain the title compound 4-97 in 44% yield as orange powder, m. p. 216-218° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 8.125 (m, 1H, Ar—H), 7.819 (m, 2H, Ar—H), 7.689 (m, 1H, Ar—H), 6.877 (m, 1H, CH), 6.620 (m, 1H, CH), 6.081 (d, 1H, J=1.5 Hz, 3-H), 5.926 (dq, 1H, J=3.3 Hz, 9.0 Hz, CH), 4.774 (m, 1H, 10-H), 2.695 (m, 2H, 4-CH ₂CH₂CH₃), 1.996 (m, 2H, 11-CH₂), 1.476 (d, 3H, J=6.3 Hz, 10-CH₃), 1.301 (m, 2H, 4-CH₂CH ₂CH₃), 0.551 (m, 3H, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 448.2 [M+H]⁺ (MW=447.45);

Anal. Calcd. for C₂₅H₂₁NO₇.5H₂O: C, 55.86; H, 5.81. Found: C, 56.05; H, 5.89.

And the title compound 4-98 was obtained simutaiously in this method.

Example 98 8-ethoxyl-4-n-propyl-6-(o-nitrophenyl)-10-methyl-4-n-propyl-7,8,10,11-tetrahydro-6H-benzo[2,3-f;2′,3′-h]-tripyranyl-2,12-dione (4-98, R₁═C₂H₅, R₂═H, R₃═CH₃, R₄═R₆═H, R₅=Ph-NO₂, R₇═H, R₈═OC₂H₅)

It is white powder, yield 25%, m. p. 237-240° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.874 (m, 1H, Ar—H), 7.469 (m, 2H, Ar—H), 7.204 (m, 1H, Ar—H), 6.165 (d, 1H, J=4.2 Hz, 3-H), 5.513 (m, 1H, CH), 4.584 (m, 1H, CH), 4.484 (m, 1H, 10-H), 3.895 (m, 1H, CH), 3.685 (m, 1H, CH), 2.957 (m, 2H, 4-CH ₂CH₂Cl₃), 2.541 (m, 2H, 11-CH₂), 2.198 (m, 2H, CH₂), 1.657 (m, 2H, 4-CH₂CH ₂CH₃), 1.138 (m, 3H, CH₃), 0.983 (t, 3H, J=7.2 Hz, CH₃), 0.814 (d, 3H, J=6.3 Hz, CH₃);

ESI-MS (m/z): 494.1 [M+H]⁺ (MW=493.52);

Example 99 4-n-propyl-6-(o-aminophenyl)-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione (4-99, R₁=n-C₃H₇, R₂═H, R₃═CH₃, R₄═R₆═H, R₅=Ph-NH₂)

Using the same procedure as described in the preparative method of compound 4-23. Compound 4-97 was treated with 15 equivlent SnCl₂. The title compound 4-99 can be produced as yellow powder in 81% yield, m. p. 175-177° C.

¹H-NMR (300 MHz, DMSO-d₆, ppm): 7.762 (m, 1H, Ar—H), 7.258 (m, 1H, Ar—H), 6.944 (m, 1H, Ar—H), 6.594 (m, 2H, Ar—H), 6.055 (s, 1H, 3-H), 5.936 (br, NH₂), 4.800 (m, 1H, CH), 4.358 (m, 1H, CH), 2.893 (t, 2H, J=7.5 Hz, 4-CH ₂CH₂CH₃), 2.633 (m, 2H, 11-CH₂), 2.108 (m, 2H, CH₂), 1.569 (dd, 3H, J=6.3 Hz, 13.2 Hz, CH₃), 0.973 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 418.1 [M+H]⁺ (MW=417.47);

HRESIMS obsd. m/z 418.1652, calcd. for C₂₅H₂₄NO₅ ⁺ 418.16544.

Example 100 10,10-dimethyl-8-n-propyl-3,4-dihydro-10H-benzo[2,3-f;2′,3′-h]-dipyranyl-2,6-dione (4-100, R₁=n-C₃H₇, R₂═H, R₅═R₆═CH₃)

(1) 5-hydroxy-4-n-propyl-9,10-dihydro-benzo[2,3-f]-pyranyl-2,8-dione (5a-100)

Compound 6-11 was mixed with 1 equivlent acrylic acid and CF₃SO₃H, the mixture was stirred for 4 hours at 60° C. in oil-bath. After cooled, the reaction solution was poured into ice-water, stirred, extrated with ethyl acetate, concentrated and dried, then purified through chromatography on silica gel to obtained 5-hydroxy-4-n-propyl-9,10-dihydro-benzo[2,3-f]-pyranyl-2,8-dione (5a-100) as off-white powder in 65% yield, m. p. 166-167° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 11.034 (s, 1H, 5-OH), 6.600 (s, 1H, 6-H), 6.053 (s, 1H, 3-H), 2.852 (m, 6H,4,9,10-CH₂), 1.571 (m, 2H, 4-CH₂CH ₂CH₃), 0.969 (t, 3H, J=7.2 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 275.1 [M+H]⁺ (MW=274.27);

Anal. Calcd. for C₁₅H₁₄O₅: C, 65.69; H, 5.15. Found: C, 65.45; H, 5.20.

HRESIMS obsd. m/z 275.0918, calcd. for C₁₅H₁₅O₅ ⁺ 275.09195.

(2)

10,10-dimethyl-8-n-propyl-3,4-dihydro-10H-benzo[2,3-f;2′,3′-h]-dipyranyl-2,6-dione (4-100, R₁=n-C₃H₇, R₂═H, R₅═R₆═CH₃)

Using the same procedure as described in the preparative method of compound 4-1, except for using compound 5a-100 and o-nitrophenyl(ethyl)acetal as starting material to obtain the title compound 4-100 in 72% yield as off-white powder, m. p. 132-135° C.

¹H-NMR (400 MHz, DMSO-d₆, ppm): 6.841 (d, 1H, J=10.0 Hz, 8-H), 6.104 (s, 1H, 3-H), 5.684 (d, 1H, J=10.0 Hz, 7-H), 2.968 (m, 4H, CH₂), 2.786 (m, 2H, 11-CH₂), 1.623 (m, 2H, 4-CH₂CH ₂CH₃), 1.508, 1.480 (2s, 6H, CH₃), 1.047 (t, 3H, J=6.4 Hz, 4-CH₂CH₂CH ₃);

ESI-MS (m/z): 341.1 [M+H]⁺ (MW=340.37);

HRESIMS obsd m/z 341.1370, calcd for C₂₀H₂₁O₅ ⁺ 341.1389.

5a-101 5-(p-tolyl)sulfonyloxy-8-methyl-4-n-propyl-2H-benzo[2,3-f]dipyranyl-2,10-dione (R1=R₁=n-C₃H₇, R3=CH₃,)

Compound 5a-11 (1 mmol) was reacted with 3 equivlent p-tolyl-sulfonyl chloride, the title compound 5a-101 was obtained in 84% yield as white powder crystalline, m. p. 258-260° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 7.897 (dd, 2H, J=1.8 Hz, 7.8 Hz, 14-Ar—H), 7.550 (d, 2H, J=7.8 Hz, 15-Ar—H), 6.696 (s, 1H, 6-H), 6.230 (s, 1H, 3-H), 4.797 (m, 1H, J=3.6 Hz, 6.3 Hz, 11.7 Hz, 8-H), 2.805 (dd, 1H, J=11.7 Hz, 16.5 Hz, 9-He), 2.688 (dd, 1H, J=3.6 Hz, 16.5 Hz, 9-Ha), 2.661 (dt, 2H, J=3.3 Hz, 8.1 Hz, 11-CH₂), 2.441 (s, 3H, 16-CH₃), 1.418 (d, 3H, J=6.3 Hz, 8-CH₃), 1.390 (m, 2H, 12-CH—), 0.758 (t, 3H, J=7.2 Hz, 13-CH₃);

ESI-MS (m/z): 443.1 [M+H]⁺ (MW=442.49);

5a-102 5-(p-tolyl)sulfonyloxy-8-methyl-4-n-propyl-2-thio-2H-benzo[2,3-f]dipyranyl-2,10-dione

Compound 5a-101 (0.5 mmol) was reacted with 5 equivlent P₂S⁵, the title compound 5a-102 was obtained in 74% yield as brown-yellow powder, m. p. 224-226° C.

¹H NMR (300 MHz, DMSO-d₆, ppm): 7.910 (dd, 2H, J=1.8 Hz, 6.6 Hz, 14-Ar—H), 7.551 (dd, 2H, J=0.6 Hz, 8.4 Hz, 15-Ar—H), 7.054 (s, 1H, 3-H), 6.785 (s, 1H, 6-H), 4.840 (m, 1H, J=11.7 Hz, 3.6 Hz, 6.3 Hz, 8-H), 2.836 (dd, 1H, J=11.7 Hz, 16.2 Hz, 9-He), 2.718 (dd, 1H, J=3.6 Hz, 16.2 Hz, 9-Ha), 2.619 (dt, 2H, J=2.4 Hz, 7.2 Hz, 11-CH₂), 2.440 (s, 3H, 16-CH₃), 1.434 (d, 3H, J=6.3 Hz, 8-CH₃), 1.384 (m, 2H, 12-CH₂), 0.754 (t, 3H, J=7.2 Hz, 13-CH₃);

ESI-MS (m/z): 458.9 [M+H]⁺ (MW=458.56).

Pharmacological Experiment

Experiment 1

Inhibitory activity of the coumarin derivatives of the present invention against HIV-1.

Inhibitory activity of the compounds against HIV-1 is assayed using the literature method. The experimental conditions, procedures, reagents and so on of the experiment are referred to the reference of “ZHIWEI CHEN, PEI ZHOU, DAVID D. HO, et al. Genetically divergent strains of simian immuno-deficiency virus use CCR5 as a coreceptor for entry. Journal of Virology, 1997, 71(4): 2705-2714”.

The results of the anti-HIV-1 activity of some compounds described in the present invention are shown in the table 1. It is indicated that some compounds give similar activity potency against HIV-1 in vitro to the parent natural compound (+)-calanolide A. It is especially interesting that three compounds (example 14, 57 and 70) exhibit the much higher inhibitory activity compared to the natural product of (+)-calanolide A and also with high therapeutic index.

TABLE 1 inhibitory activity of compounds against HIV-1. Anti-HIV (%, Cell toxicity Compd 1.0 μM) (10 μM) EC₅₀ (TI) (+)-11-demethyl 75% 54 (++) — Calanolide A (+)-Calanolide A 86%  6 (+) 100-200* Example 7 48.3 − — Example 9 73.2 − 0.27 μM (>1000) Example 11 73.1 − 0.11 μM (818) Example 12 68.3 0.64 μM (47-140) Example 13 64.9 − — Example 14 61.9 + 32.5 nM (102-308) Example 15 46.4 + — Example 16 62.7 + — Example 17 57 − — Example 18 40 + — Example 19 59.3 + — Example 20 68.1 − 0.37 μM (243-730) Example 22 51.9 − — Example 24 58 − — Example 27 67 − — Example 29 73.1 − 0.11 μM (818) Example 30 38.9 ++ — Example 31 45.3 ++ — Example 34 54.1 − — Example 44 96.4 ++ — Example 45 96.4 ++ — Example 46 96.7 ++ — Example 47 97 ++ — Example 50 96.3 +++ — Example 57 93.5 − 2.85 nM (>10526) Example 70 68.6 − 14.1 nM (709-2127) Example 73 53.6 − — Example 74 47.6 − — Example 75 62.4 ++ — Example 76 37.8 − — Example 77 35.2 + — Example 79 57.4 − — Example 81 55.7 − — Example 82 75.4 − — Example 83 39.5 − — Example 86 57.3 − — Example 87 56.4 − — Example 88 46.2 − — Example 91 49.1 − — Example 92 47.1 − — Example 96 51.7 − — Example 97 52.6 − — Example 98 61 + — Therapeutic index (TI) = 50% cytotoxicity doses/50% effective dose; “+”, “++”, “+++” indicate that <10%, 10-80%, >80% of the host cells of the virus died at the concentration of 10 μmol of the tested compounds, respectively; *J. Med. Chem. 1996, 39(6):1303-13.

Experiment 2

Activity of the compounds of the present invention against Mycobacterium tuberculosis

The results of the anti-Mycobacterium tuberculosis activity of the novel synthetic dipyranyl coumarin compounds and some of their synthetic intermediate described in the present invention are shown in the table 2 (“Antimycobacterial data were provided by the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) through a research and development contract with the U.S. National Institute of Allergy and Infectious Diseases”. The screen was conducted against Mycobacterium tuberculosis H37Rv (ATCC 27294) in BACTEC 12B medium using the Microplate Alamar Blue Assay (MABA), Control compound (Amikacin): Activity: Avg MIC₅₀=0.09 μg/mL−Avg MIC₉₀=0.12 μg/mL).

It is defined that the compound which MIC₉₀ value is less than 10 μg/mL is indicated as anti-TB active compound. Wherein examples 14, 25, 34, 37, 39, 40, 41, 42, 45, 46, 47, 49, 50, 51, 53, 55, 70, 74, 75, 80, 85, 6-71, 5b-16, 5a-101, 5a-102 are novel anti-TB active compounds.

TABLE 2 Activity of the compounds against TB. Examples Assay MIC₉₀ (μg/mL) IC₅₀ (μg/mL) Example 1 MABA 59.459 39.192 Example 2 MABA 35.17 20.319 Example 3 MABA >100 33.37 Example 4 MABA >100 7.517 Example 6 MABA >100 52.447 Example 14 MABA 6.437 5.723 Example 16 MABA >100 2.912 Example 18 MABA >100 46.75 Example 19 MABA 11.246 7.946 Example 21 MABA >100 16.626 Example 23 MABA 27.6 24.193 Example 25 MABA 3.898 2.858 Example 26 MABA 43.608 23.88 Example 32 MABA >100 78.299 Example 34 MABA 3.183 2.875 Example 36 MABA 36.586 24.248 Example 37 MABA 8.36 5.332 Example 38 MABA 14.419 10.417 Example 39 MABA 9.936 5.089 Example 40 MABA 2.47 1.584 Example 41 MABA 3.268 2.918 Example 42 MABA 6.807 5.561 Example 43 MABA 10.791 6.42 Example 45 MABA 2.726 2.012 Example 46 MABA 0.716 0.276 Example 47 MABA 1.729 1.493 Example 49 MABA 6.396 4.619 Example 50 MABA 6.695 6.072 Example 51 MABA 0.496 <0.2 Example 52 MABA 13.402 11.778 Example 53 MABA 6.847 6.096 Example 54 MABA 61.792 36.518 Example 55 MABA 1.07 <0.2 Example 56 MABA >100 62.338 Example 57 MABA 1.754 0.825 Example 58 MABA 54.902 34.498 Example 60 MABA >100 32.547 Example 61 MABA >100 17.198 Example 68 MABA 44.884 32.994 Example 70 MABA 5.543 3.307 Example 74 MABA 6.379 5.701 Example 75 MABA 1.891 1.005 Example 78 MABA >100 98.967 Example 79 MABA 6.837 6.067 Example 80 MABA 5.458 3.42 Example 82 MABA 56.155 36.254 Example 83 MABA 27.67 24.407 Example 84 MABA 27.688 17.292 Example 85 MABA 4.861 2.08 Example 87 MABA >100 51.239 Example 88 MABA >100 70.653 Example 93 MABA >100 76.155 Example 94 MABA 16.67 10.005 Example 95 MABA 34.469 20.105 Example 96 MABA 22.233 11.104 Example 99 MABA 15.494 7.486 6-71 MABA 4.06 2.526 5b-16 MABA 5.406 4.312 6-36 MABA 14.434 11.348 5b-21 MABA 21.303 14.865 5a-31 MABA 23.472 16.991 6-26 MABA 24.358 9.97 5a-16 MABA 25.136 22.507 5a-71 MABA 29.922 15.447 5a-20 MABA 41.962 26.946 5a-13 MABA 53.43 46.748 5a-14 MABA 85.832 60.245 5a-7 MABA 94.977 59.798 5b-14 MABA >100 6.586 5a-15 MABA >100 66.008 5a-19 MABA >100 83.08 5b-11 MABA >100 95.261 5b-1 MABA >100 43.07 5a-27 MABA >100 94.349 5b-3 MABA >100 90.516 5a-101 MABA 6.663 4.2 5a-102 MABA 6.241 5.48 

1. A compound of general formula (I):

or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein:

in ring C is either a carbon-carbon single bond or a carbon-carbon double bond;

in ring C is a carbon-carbon single bond or no bond;

in ring D is either a carbon-carbon single bond or a carbon-carbon double bond; X is O or S; R₁ is cyano, C₁₋₆alkyl, C₁₋₆alkyl substituted by one or more halogen, C₃₋₆cycloalkyl, C₁₋₆ alkyl substituted by phenyl, or C₁₋₆alkyl substituted by heterocyclyl, wherein the said phenyl group or heterocyclic group may each be unsubstituted or substituted by one or more substituents selected from the group consisting of C₁₋₆alkyl, C₁₋₆alkoxyl, nitro, amino, cyano, halogen; R₂ is H, halogen, cyano, C₁₋₆alkyl, C₁-C₆alkyl substituted by one or more halogen, C₁₋₆alkyl substituted by phenyl, or C₁₋₆alkyl substituted by heterocyclyl, wherein the said phenyl group or heterocyclic group may each be unsubstituted or substituted by one or more substituents selected from the group consisting of C₁₋₆alkyl, C₁₋₆alkoxyl, nitro, amino, cyano, halogen; or R₁ and R₂ together with the ring B may form a 5- or 6-member saturated alicyclic ring; R₃ is H, C₁₋₆alkyl, aryl, or a methylene substituted by one or more substituents selected from the group consisting of halogen, cyano, azido, amino, substituted amino, and substituted aminoamide, substituted sulfonylamide, substituted ureido, substituted thioureido, substituted guanidino groups and substituted groups being selected from aryl or alkyl; R₄ is H, methyl or ethyl, with the proviso that when R₁ is phenyl and R₂ is H, R₃ and R₄ are methyl groups where R₃ and R₄ are trans or cis; when R₄ is H and

in ring C is a carbon-carbon single bond, R₃ may be a dimethyl group; furthermore, R₃ and R₄ may, together with the carbon atom C₁₀ and C₁₁ to which they are each attached, form an additional 3-member and/or 6-member saturated carbon ring; R₅ and R₆ are independently selected from the group consisting of H, C₁₋₆alkyl, alkenyl, and phenyl group substituted by nitro, amino, cyano, or halogen; R₇ is H or C₁₋₆alkyl; R₈ is H or C₁₋₆ alkoxyl; with the proviso that when

in ring D is a carbon-carbon single bond, R₈ is alkoxyl; when R₇ and R₈ are H,

in ring D is a carbon-carbon double bond.
 2. The compound of claim 1, wherein when

in ring C represents no bond, the compound has general formula 1′:

wherein Y is isopropyl, 2-methylenepyridinyl or 2-methylenefuranyl.
 3. The compound of claim 1, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein X is O or S, both of R₅ and R₆ are methyl group,

in ring C is a carbon-carbon single bond.
 4. The compound of claim 3, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₁ is C₁₋₆alkyl, R₂ is H or halogen, R₄ is H.
 5. The compound of claim 4, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₃ is dimethyl group.
 6. The compound of claim 3, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₁ and R₂, together with the carbon atom to which they are each attached, form a 5- or 6-member ring.
 7. The compound of claim 3, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₁ is C₁₋₆ alkyl, R₂ is H, R₃ and R₄, together with each other or together the carbon atom to which they are each attached, form a 3- or 6-member ring.
 8. The compound of claim 1, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein X is O, both of R₅ and R₆ are methyl group,

in ring C is a carbon-carbon double bond.
 9. The compound of claim 1, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein X is S, both R₅ and R₆ are methyl group, the bond in ring C between the carbon connected with R₃ and the carbon connected with R₄ is a carbon-carbon single bond.
 10. The compound of claim 1, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₁ is C₁₋₆ alkyl, aryl or substituted nitrogen-containing heterocycle ring, R₂ is H or halogen, R₃ is methyl, R₄ is H, one of R₅ and R₆ is H and the other is C₁₋₆alkyl or nitro, amino, or halogenated phenyl,

in ring C is a carbon-carbon single bond.
 11. The compound of claim 1, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₁ is C₁₋₆alkyl, aryl or substituted nitrogen-containing heterocycle ring, R₂ is H or halogen, R₃ is methyl, R₄ is H, both of R₅ and R₆ are H,

in ring D is either a carbon-carbon single bond or a carbon-carbon double bond, R₇ is methyl, R₈ is H or ethoxyl.
 12. The compound of claim 1 or an optical isomer, pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of: 4,6,6,10-tetramethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 3,4,6,6,10-pentamethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4,6,6,10-tetramethyl-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4,6,6,10-tetramethyl-3-benzyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-chloromethylene-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-piperazinylmethylene-10,11-dihydro-2H,6H,12H-benzo[2,3-f:2′3′-h]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-p-methylpiperazinylmethylene-10,11-dihydro-6H-benzo[2,3-f:2′3′-h]-tri pyranyl-2,12-dione 6,6,10-trimethyl-4-trifluoromethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-ethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-ethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-6H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4,10-di-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-n-pentyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-p-methyl-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10,11-trans-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10,11-cis-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-3-chrolo-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-p-nitrophenyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-p-aminophenyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-(3,4,5-trimethoxyl)-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-(3-(2,6-dichloro-5-fluoro)pyridinyl)-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-3,4-cyclopentyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-3,4-cyclohexyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 2,10,10-trimethyl-8-n-propyl-6-thio-2,3-dihydro-6H, 10H-benzo[2,3-f:2′,3′-h]-tripyranyl-4-one 6,6,10-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,11-trimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-3-fluoro-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 10-methyl-3-fluoro-4,6-di(-n-propyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-3-fluoro-4-n-propyl-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4,6-di(-n-propyl)-2H,6H,12H-benzo[1,2-b: 3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-propyl-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 10-methyl-6-n-propyl-4-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4,6-di(n-butyl)-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-ethyl-6-n-propyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-ethyl-6-n-butyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,2-dione 10-methyl-4-n-propyl-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-ethyl-6-phenyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-propyl-6-phenyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-butyl-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-ethyl-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-ethyl-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-ethyl-6-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 10-methyl-4,6-di(-n-propyl)-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-propyl-3-chloro-6-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-propyl-3-chloro-6-phenyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 11-methyl-4,6-di(-n-propyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-propyl-6-ethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4,6-diethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-propyl-6-ethyl-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4,6-diethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10-methyl-4-n-propyl-6-ethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-n-propyl-10-bromomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-n-propyl-10-azidomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-n-propyl-10-aminomethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6,10-trimethyl-4-n-propyl-10-hydroxymethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-(p-fluorophenylureido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-(p-acetylaminophenylsulfonamido)methylene-2H,6H, 12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-(p-fluorophenylsulfonamido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-(p-methoxylphenylsulfonamido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-(o-methoxyl-phenylureido)methylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-tetrahydropyrrolylmethylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,6-dimethyl-4-n-propyl-10-piperidinylmethylene-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 5-hydroxy-6-(1′-isopropyl-1′ H-pyrrol-2′-ene)-2,2-dimethylene-10-n-propyl-2H-benzo[2,3-f]-pyranyl-8-one 5-hydroxy-6-(1′-(2-pyridyl)methylene-1′H-pyrrol-2′-ene)-2,2-dimethyl-10-n-propyl-2H-benzo[2,3-f]-pyranyl-8-one 5-hydroxy-6-(1′-(2-furanyl)methylene-1′H-pyrrol-2′-ene)-2,2-dimethyl-10-n-propyl-2H-benzo[2,3-f]-pyranyl-8-one 6,6,-dimethyl-4-n-propyl-10,11-cis-cyclopropyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]tripyranyl-2,12-dione 6,6,10-trimethyl-4-(3,3′,3″-trifluoromethyl)-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-(3,3′,3″-trifluoro-n-propyl)-6-propenyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-(3,3′,3″-trifluoron-n-propyl)-6-n-butyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-(3,3′,3″-trifluoro-n-propyl)-6-phenyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 6,11-dimethyl-4-n-propyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-6-propenyl-11-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-6-n-butyl-11-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-6-phenyl-11-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-12-dione 6,10-dimethyl-4-ethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,10-dimethyl-4-n-propyl-3-chloro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,10-dimethyl-4-n-butyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,10-dimethyl-4-ethyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 6,10-dimethyl-4-n-propyl-3-fluoro-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-6-propenyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-6-propenyl-3-chloro-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-ethyl-6-propenyl-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-ethyl-6-propenyl-3-fluoro-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-ethyl-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′: 5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-3-chloro-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-n-propyl-3-fluoro-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 4-ethyl-3-fluoro-7,10-dimethyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 8-ethyoxyl-7,10-dimethyl-4-ethyl-7,8,10,11-tetrahydro-6H-benzotripyran[2,3-f;2′,3′-h]-2,12-dione 8-ethyoxyl-7,10-dimethyl-4-n-propyl-7,8,10,11-tetrahydro-6H-benzotripyran[2,3-f;2′,3′-h]-2,12-dione 8-ethoxyl-7,10-dimethyl-4-n-propyl-3-chloro-7,8,10,11-tetrahydro-6H-benzotripyran[2,3-f;2′,3′-h]-2,12-dione 4-n-propyl-6-(o-nitrophenyl)-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 8-ethoxyl-6-(o-nitrophenyl)-10-methyl-4-n-propyl-7,8,10,11-tetrahydro-6H-benzotripyran[2,3-f;2′,3′-h]-2,12-dione 4-n-propyl-6-(o-aminophenyl)-10-methyl-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6-b″]-tripyranyl-2,12-dione 10,10-dimethyl-8-n-propyl-3,4-dihydro-10H-benzo[2,3-f;2′,3′-h]-dipyranyl-2,6-dione.
 13. A compound of general formula (II):

or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₁-R₄ are as defined in claim 1; M is p-methylphenylsulfonyl or C₁₋₄ alkyl.
 14. The compound according to claim 13, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of: benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-3,4,8-trimethyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-3-chloro-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-3-benzyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-chloromethylene-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-trifluoromethyl-8-methyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-8-methyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-3-fluoro-8-methyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-methyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8,8-dimethyl-4-n-propyl-2,10-dione 5-hydroxyl-4-n-butyl-benzo[2,3-f]-pyranyl-2,3-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4,8-di(n-propyl)-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-n-pentyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-phenyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-p-methyl-phenyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8,9-trans-cyclohexyl-2,10-dione 6,6-dimethyl-4-n-propyl-10,11-cis-cyclohexyl-2,12-dione benzo[1,2-b:3,4-b′:5,6-b″]-dipyranyl-5-hydroxyl-8-methyl-3-chloro-4-n-propyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-phenyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-p-nitrophenyl-2,10-dione benzo[1,2-b: 3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-(3,4,5-trimethoxyl)-phenyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-(3-(2,6-dichloro-5-fluoro) pyridinyl)-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3,4-cyclopentyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3,4-cyclohexyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-fluoro-4-n-propyl-10-one benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-butyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-9-methyl-4-n-propyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-bromomethyl-4-n-propyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-5-hydroxyl-8-azidomethyl-4-n-propyl-2,10-dione benzo[1,2-b:3,4-b′]-dipyranyl-4-5-hydroxyl-8-methyl-((3,3′,3″-trifluoro)-n-propyl)-2,10-dione 5-hydroxy-4-n-propyl-9,10-dihydro-benzo[2,3-f]-pyranyl-2,8-dione 5-(p-methylphenyl)-sulfonyloxy-8-methyl-4-n-butyl-2H-benzo[2,3-f]dipyranyl-2,10-dione 5-(p-methylphenyl)-sulfonyloxy-8-methyl-4-n-butyl-2-thio-2H-benzo[2,3-f]dipyranyl-2,10-dione.
 15. A compound of general formula (III):

or an optical isomer, pharmaceutically acceptable salt or solvate thereof, wherein R₁—R₄ are as defined in claim 1; M is p-methylphenylsulfonyl or C₁₋₄ alkyl.
 16. The compound according to claim 15, or an optical isomer, pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of: benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4,8-dimethyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4,8-diimethyl-3-chloro-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4,8-diimethyl-3-benzyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4-trifluoromethyl-8-methyl-2,6-dione benzo[1,2-b: 5,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-8-methyl-2,6-dione benzo[1,2-b: 5,4-b′]-dipyranyl-5-hydroxyl-4-ethyl-3-fluoro-8-methyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-methyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4,8-di(n-propyl)-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-phenyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-chloro-4-n-propyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-phenyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-p-nitrophenyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-3-fluoro-4-n-propyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-methyl-4-n-butyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-8-bromomethyl-4-n-propyl-2,6-dione benzo[1,2-b:5,4-b′]-dipyranyl-5-hydroxyl-4-n-propyl-8-methyl-2-thio-2,6-dione.
 17. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of any one of claims 1 to 16 or an optical active substance, pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier or excipient.
 18. Use of a compound of any one of claims 1, 13 or 15 for the manufacture of a medicament for treatment or prevention of disease relative to HIV-1 infection.
 19. Use of a compound of any one of claims 1, 13 or 15 for the manufacture of a medicament for treatment or prevention of disease relative to TB infection.
 20. A process for preparing a tetracyclic coumarin compound of general formula below, which is characterized in that the compound with ring D is obtained from a tricyclic coumarin compound with rings A, B and C under microwave irradiation as the chemical reaction below:

wherein R₁-R₆ are as defined in claim
 1. 21. A process for preparing a tetracyclocoumarin compound (4), which is characterized in that a tricyclic coumarin compound 14 with rings A, B and D is reacted with acyl halide of α,β-unsaturated acid to form ring C:

wherein R₁-R₇ are as defined in claim
 1. 22. A process for preparing the compound of claim 2, which is characterized in that when the tetracycliccoumarin compound of claim 1 in which R₃ is CH₂Br group is reacted with primary amines, a rearrangement reaction occurs leading to ring C being opened while the structure of tricyclic ring A, B, and D is unchanged,

wherein Y is as defined in claim
 2. 23. A process for preparing the compound of claim 1 in which X is S, characterized in that the compound is synthesized through the construction of ring D from a tricyclic coumarin compound with rings A, B and C according to the process of claim 15:

wherein, R₁-R₈ are as defined in claim
 1. 